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Biomedical subjects

P Almqvist

Publications and source records attributed to P Almqvist.

At least 19 recordsLinked to original sources
PubMed2006

Improved migraine management in primary care: results of a patient treatment experience study using zolmitriptan orally disintegrating tablet.

The 'Zomig Appropriate for Primary care' programme was developed to address the needs of primary care physicians (PCPs) to improve migraine management. As part of the programme, an international, open-label, 6-month clinical study was performed. The study included new and tangible outcome variables relevant to PCPs and recruited patients presenting in primary care with an established migraine diagnosis. Patients treated up to three migraine attacks per month with zolmitriptan orally disintegrating tablet (ODT) 2.5 mg. All other migraine attacks occurring during the study period were treated with the patient's usual migraine medication (including other triptans). Questionnaires were used to record patient treatment experiences at the study end. The primary end-point was the proportion of patients wanting to continue using zolmitriptan ODT. Some 595 patients treated 7171 migraine attacks with zolmitriptan ODT. Of the 504 patients who completed the 6-month questionnaire, 380 (75.4%) wished to continue using zolmitriptan ODT. The results of the study indicate that patient-orientated end-points are more motivational and meaningful to physicians than traditional end-points used in controlled clinical trials, allowing them to make informed decisions regarding migraine management.

Administration, Oral↗
PubMed2000

Implantation of bioactive growth factor-secreting rods enhances fetal dopaminergic graft survival, outgrowth density, and functional recovery in a rat model of Parkinson's disease.

One of the drawbacks with fetal ventral mesencephalic (VM) grafts in Parkinson's disease is the limited outgrowth into the host striatum. In order to enhance graft outgrowth, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were administered by implantation of bioactive rods to the lateral part of the striatum to support grafted fetal VM implanted to the medial portion of the striatum. The polymer-based bioactive rods allow for a local secretion of neurotrophic factors over a time period of approximately 2 weeks. Moreover, glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-beta1 (TGFbeta1) were administered using the same technique. Concomitant administration of GDNF and TGFbeta1 was achieved by insertion of one GDNF and one TGFbeta1 rod. This was performed to investigate possible additive effects between GDNF and TGFbeta1. Rotational behavior, outgrowth from and nerve fiber density within the VM graft, and the number of TH-positive cells were studied. Functional compensation by reduction of rotational behavior was significantly enhanced in animals carrying bFGF and GDNF rods in comparison with animals carrying only VM graft. EGF and bFGF significantly increased the innervation density. Moreover, the nerve fiber density within the grafts was significantly enhanced by bFGF. Cell counts showed that a significantly higher number of TH-positive neurons was found in grafts treated with bFGF than that found in GDNF-treated grafts. An additive effect of TGFbeta1 and GDNF was not detectable. These results suggest that bioactive rods is a useful tool to deliver neurotrophic factors into the brain, and since bFGF was a potent factor concerning both functional, immunohistochemical and cell survival results, it might be of interest to use bFGF-secreting rods for enhancing the overall outcome of VM grafts into patients suffering from Parkinson's disease.

Animals↗
PubMed1997

Adult nestin-expressing subependymal cells differentiate to astrocytes in response to brain injury.

The adult brain contains a small population of central nervous system (CNS) cells in the subependyma which, like embryonic CNS progenitor cells, express the intermediate filament nestin. In this report, the differentiation capacity in vivo of these cells was analysed following a standardized trauma. Before the trauma, the subependymal cells expressed nestin but not the astrocytic and neuronal differentiation markers glial fibrillary acidic protein (GFAP) and neurofilament respectively. In response to injury, the majority of the subependymal cells coexpressed nestin and GFAP, but never nestin and neurofilament. Furthermore, cells coexpressing nestin and GFAP were found progressively further away from the subependyma and closer to the lesion at later time points after the injury, indicating that these cells migrate towards the lesion. Nestin was in addition re-expressed in reactive astrocytes near the lesion and in non-reactive astrocytes very far from the lesion throughout the ipsilateral cortex. In conclusion, our data indicate that the nestin-positive subependymal cells are an in vivo source for the generation of new astrocytes but not neurons after injury, and that nestin re-expression in astrocytes following traumatic stimuli can be used as a sensitive marker for astroglial activation.

Animals↗
PubMed1995

Timing of antibiotic treatment in non-perforated gangrenous appendicitis.

OBJECTIVE: To assess whether antibiotic treatment with cefuroxime and tinidazole started during the operation was as effective as treatment started before operation in patients with gangrenous non-perforated appendicitis. DESIGN: Prospective randomised study. SETTING: University hospital, Sweden. SUBJECTS: 114 patients with gangrenous, non-perforated appendicitis who had had antibiotics started before operation and 120 whose treatment was started during operation out of a total of 575 who presented with a presumptive diagnosis of appendicitis. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: There were no deaths, and the rates of infective complications were 1/114 (0.9%) and 3/120 (3%), respectively. The median hospital stay was four days in both groups. CONCLUSION: Antibiotic treatment started during the operation is not significantly worse at preventing infective complications in non-perforated, gangrenous appendicitis than treatment started before the operation.

Acute Disease↗
PubMed1994

Morphology and growth of embryonic, human dorsal root ganglion explants in long-term culture: expression of cell type-specific markers during early differentiation.

Embryonic, human spinal ganglion explants were plated at 5-12 weeks postconceptional age and cultured for 5-50 days on a semisynthetic substrate in a serum-containing culture medium without addition of antibiotics or preconditioned medium. The growth pattern in vitro was found to be age dependent. Five- to 6-week ganglia showed a characteristic semicircular growth pattern with bidirectional extension of neurites on top of a monolayer of supportive cells. Explanted 9- to 10-week ganglia showed an extensive, multidirectional neurite outgrowth with less pronounced proliferation of nonneuronal cells. Neurite extension, fasciculation, cell migration and morphology were studied immunohistochemically with antibodies to neurofilament (NF), S-100, and the Thy-1 glycoprotein. Both NF and S-100 were expressed at 5 weeks gestational age in ganglionic neurons and in proliferating Schwann cells in contact with axonal processes, respectively. NF was homogeneously distributed in both cell somata and neurites, whereas S-100 immunoreactivity showed an intense nuclear and a weaker cytoplasmic distribution in spindle-shaped, bipolar Schwann cells. This staining pattern was conserved during differentiation in long-term culture. Thy-1 was expressed on ganglionic neurites forming fascicles by the third week in culture. However, Thy-1 was never expressed until the total age of 10 weeks. In addition, Thy-1 was found on fibroblasts from the first week in culture. The distribution of Thy-1 on the cytoplasmic membrane was similar in both cell types, showing a coarsely granulated membrane staining. The temporal as well as the spatial expression of differentiation antigens in tissue sections of early embryonic spinal cord and spinal ganglia were very similar to what was observed in vitro.

Antigens, Surface↗
PubMed1994

Radiology in laparoscopic cholecystectomy. A retrospective study.

Laparoscopic cholecystectomy (LC) is attempted in all our patients scheduled for cholecystectomy. The related standard radiologic procedures are preoperative ultrasonography (US) and preoperative cholangiography (PCA). In a retrospective study of 214 patients scheduled for LC over a 2-year period we have reviewed the radiologic and clinical records. Preoperative US revealed stones in the common bile duct (CBD) in 8 patients, all treated with endoscopic papillotomy before or after operation. PCA was successful in 176 patients (82%) and gave crucial information in 22 patients including 8 with stones in the CBD not preoperatively diagnosed, 6 with anomalous anatomy, and 8 with malpositioned surgical clip on the cystic duct. In 26 patients LC was converted into open surgery, but in only one case due to CBD stone revealed at PCA. Seventeen patients had minor postoperative complications, all managed conservatively. We consider preoperative US and PCA appropriate radiologic investigations in conjunction with LC.

Bile Ducts↗
PubMed1992

Target-specific outgrowth from human mesencephalic tissue grafted to cortex or ventricle of immunosuppressed rats.

Human fetal mesencephalic tissue was grafted to rats with unilateral lesions of the nigrostriatal pathway. The animals were immunosuppressed with cyclosporine A. Grafts were placed either into the lateral ventricle ipsilateral to the lesion or in the cingulate cortex above corpus callosum. The grafts and newly formed fibers were visualized by immunohistochemistry with antibodies against tyrosine hydroxylase (TH) and the human Thy-1 glycoprotein. TH-positive fibers covered the total volume of striatum when the graft was placed either in the ventricle or in the cortex. When the transplant was located in the ventricle, TH-positive cells migrated from the graft into host striatum. No cell migration was seen into any other areas than striatum. Cortex and septum were sparsely reinnervated by the graft, but not to a density higher than that normally seen. Globus pallidus was totally devoid of TH-positive fibers. When the graft was placed in cingulate cortex, fiber bundles penetrated through corpus callosum into either striatum, to arborize in its dorsal parts, or followed the medial side of the lateral ventricle to ventral limbic areas, where a fiber network also was formed. Human specific Thy-1-immunohistochemistry revealed positivity only on the lesioned side. These data suggest that dopamine neurons in human mesencephalic tissue, grafted to the rat brain, can migrate specifically into host striatum. Furthermore, TH-positive fiber outgrowth occurred only into dopamine denervated areas of the host, avoiding areas that are normally not innervated by nigral neurons, but also able to reach distant target cells.

Animals↗
PubMed1992

Laparoscopic cholecystectomy in a patient with hemophilia B.

Surgical procedures in hemophiliacs is a demanding challenge for the surgeon and hematologist. This report deals with a successful laparoscopic cholecystectomy in a young patient with hemophilia B. Despite a prolonged operation time, because of a partially intrahepatic gallbladder, no bleeding complications were registered and the patient recovered well. Laparoscopic cholecystectomy seems to be the method of choice in hemophiliacs, as it minimizes tissue trauma. Nevertheless, the procedure should be performed only in specialized centers with a fully equipped coagulation laboratory and a team of surgeons and hematologists familiar with the special problems of surgery in hemophiliacs.

Adult↗
PubMed1991

Splanchnic oxygen consumption in septic and hemorrhagic shock.

Oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in septic shock. Local hypoxia with later secondary organ failure may develop, however, despite an often hyperdynamic circulation. The splanchnic organs seem to be of vital importance in this context. In experiments performed in pigs we compared total body VO2 and DO2 with oxygen consumption and delivery in the gastrointestinal organs and the liver in two different shock states: (1) septic shock induced by peritonitis (n = 6) and (2) hemorrhagic shock (n = 6). Another group of six animals not in shock served as controls. Total, gastrointestinal, and liver DO2 decreased in a similar pattern in both septic and hemorrhagic shock. Gastrointestinal and liver VO2 increased in sepsis, whereas it was unchanged in hemorrhage. In the later phase of sepsis, liver VO2, but not gastrointestinal VO2, again decreased, because liver oxygen extraction was almost total and liver DO2 decreased further. The development of flow-dependent liver hypoxia was reflected in a decrease in liver lactate turnover (increased liver lactate release) during late sepsis. Early hypoxia in the splanchnic region is suggested as a plausible mechanism behind the development of secondary organ failure, especially in sepsis.

Animals↗
PubMed1990

Behavioral and electrophysiological correlates of human mesencephalic dopaminergic xenograft function in the rat striatum.

While human fetal xenografts placed into immunocompromised animal hosts have been shown to survive and grow, their ability to function and influence the host tissue has not been fully examined. Therefore, we implanted grafts of human fetal mesencephalic tissue intracranially into rats with unilateral 6-hydroxydopamine lesions of their nigrostriatal dopaminergic innervation and tested the rats behaviorally for reductions in apomorphine-induced rotations. The purpose of this study was to test the ability of these grafts to provide a functional reinnervation by comparing the behavioral changes with the morphology and presence of electrophysiologically active dopaminergic neurons within the graft and with firing rates of host striatal neurons. Adult Sprague-Dawley rats that had been unilaterally lesioned and that showed a stable two peak pattern of apomorphine-induced rotations received grafts of human fetal mesencephalic tissue placed directly into the lesioned striatum. These rats were then further tested each month for five months for reductions in their turning behavior. At 5 to 6 months postgrafting, electrophysiological recordings were made of cells within the graft and within the host striatum. The rats were then examined immunohistochemically to evaluate graft survival and extent of reinnervation of the host tissue. The rats receiving mesencephalic dopaminergic grafts demonstrated a 79% reduction in their apomorphine-induced rotations. Electrophysiological recordings revealed spontaneously active dopaminergic neurons within the graft as well as host striatal cell firing rates consistent with those of dopamine-innervated cells. Furthermore, immunohistochemical studies confirmed graft survival and revealed marked fiber outgrowth from the graft into and throughout the striatum. Taken together these findings provide evidence that grafts of human fetal mesencephalic tissue are able to produce behavioral improvements in lesioned animals which are associated with the presence of dopaminergic neurons within the graft and are consistent with normal host striatal cell activity levels.

Animals↗
PubMed1990

Role of the renin-angiotensin system in liver blood flow reduction produced by positive end-expiratory pressure ventilation.

Positive end-expiratory pressure (PEEP), often used in critically ill patients, reduces cardiac output, and its adverse effects on splanchnic circulation imply a risk of regional secondary organ failure. To investigate if the renin-angiotensin system (RAS) mediates PEEP-induced circulatory changes, hemodynamic effects of PEEP were measured in four groups of pigs: controls (C), nephrectomized (N), or given enalaprilate, an angiotensin-converting enzyme inhibitor (E), or saralasin, a competitive inhibitor of angiotensin II (S). Groups N, E and S represented interference with RAS effects at different sites. With PEEP at 10 cmH2O, mean arterial pressure, cardiac index, portal venous and hepatic arterial blood flow decreased in all groups, while portal and central venous pressures rose, without significant intergroup difference. Systemic and preportal bloodflow resistance increased in groups S and N, and hepatic arterial resistance in group C. Accentuation of the flow and pressure changes occurred with 20 cm PEEP in all groups, with increase of systemic and hepatic resistance in S and N, or preportal resistance in group N and protal resistance in group C. The study suggested that RAS is not a major mediator of PEEP-induced circulatory changes. Differing responses within groups N, S and E may have been due to interference with the action of RAS and of other vasoactive substances.

Animals↗
PubMed1990

Lack of beneficial effects of milrinone in severe septic shock.

The effects of milrinone were investigated in a porcine septic shock model. Septic shock was induced by i.v. infusion of live Escherichia coli. Anesthetized pigs were treated with milrinone before the E. coli infusion or were left untreated as septic controls. E. coli caused a significant reduction of cardiac index, renal blood flow, and portal blood flow. Pulmonary vascular resistance was significantly increased, as were the systemic and preportal vascular resistances. One of the seven septic control pigs died. In milrinone-treated septic animals cardiac index was maintained for a longer period of time but blood pressure was significantly reduced compared with the control pigs. Pulmonary vasoconstriction was little affected by pre-treatment with milrinone. Four out of seven milrinone-treated pigs died during the observation period. It is concluded that in the settings of the used porcine septic shock model milrinone treatment has no beneficial effect.

Animals↗
PubMed1990

Early detection of gastrointestinal mucosal ischemia in porcine E. coli sepsis.

The aim of this study was to investigate the oxygenation of the gastrointestinal tract mucosa using indirect pH measurements in a porcine septic model (intravenous infusion of live E. coli). By means of intraluminally placed balloon catheters (Tonomitior) permeable to CO2, intramucosal pH (pHi) was calculated using the Henderson-Hasselbalch equation. Cardiopulmonary hemodynamics and portal blood flow were measured using Swan-Ganz catheters. Samples were taken from the gastrointestinal tract for histological examination. Nine pigs were given i.v. E. coli infusion while six pigs served as sham controls and were given an equivalent amount of Ringer's solution only. All septic animals developed hemodynamic signs of septic shock. Gastric, small intestinal and sigmoid colonic pHi decreased gradually during the four hour observation period. In the small intestine and the sigmoid colon the decrease was significant already after one hour (p less than 0.01 and p less than 0.02, respectively). Microscopic examination of tissue specimens obtained 4 hours following induction of sepsis revealed normal or close to normal findings in all the sham and in more than half of the septic animals. These findings indicate that abnormally low gastrointestinal intramucosal pH may be found early in septicemia, preceding microscopically detectable damage by several hours. It is concluded that the tonometer technique does provide early detection of gastrointestinal ischemia in septic shock.

Animals↗
PubMed1989

Human fetal mesencephalic tissue grafted to dopamine-denervated striatum of athymic rats: light- and electron-microscopical histochemistry and in vivo chronoamperometric studies.

Human fetal mesencephalic tissue obtained from elective first-trimester abortions was grafted to 6-hydroxydopamine-denervated striatum of athymic (nude) rats. After 3-6 months, the transplants were evaluated by light and electron microscopy using antibodies against tryosine hydroxylase (TH), human specific Thy-1 (Thy-1), 5-hydroxytryptamine (5-HT), and laminin. In vivo chronoamperometric studies of K+-induced release of electroactive species were done prior to the histochemical evaluations. At the light microscopical level, Thy-1-immunoreactivity was evenly distributed throughout the entire transplants. Thy-1-immunoreactive nerve fibers were observed radiating from the graft into the host striatum. In sections that were double-stained with antibodies against Thy-1 and TH, such nerve fibers contained both markers. Also 5-HT-immunoreactive cells were found in the grafts with processes both in the grafts and radiating into host neuropil. Laminin immunohistochemistry showed an even distribution of capillaries in the graft with less density than in host brain, suggesting immaturity of graft tissue. At the ultrastructural level, TH-immunoreactive axons made symmetric contacts with unlabeled dendritic shafts and dendritic spines within the host brain. A few asymmetric contacts with TH-immunoreactive axons were seen. 5-HT-immunoreactive terminals made both symmetric and asymmetric contacts with unlabeled dendritic shafts and spines. In vivo chronoamperometry using local application of K+ revealed average signals that were lower on the transplanted side than in control striatum. However, close to the grafts significant amounts of the K+-evoked signal amplitudes were as large as 1.3 microM, and the ratio of the reduction to oxidation currents suggested release of a mixture of dopamine and 5-HT. Taken together, this study shows that human fetal mesencephalic tissue pieces survive grafting into nude rats, develop normal vascularization, and express coexistence of TH- and Thy-1-immunoreactivity. Human TH- and 5-HT-immunoreactive nerve fibers form synapses in host striatum and release monoamine neurotransmitters.

Animals↗
PubMed1988

Characterization of a hydrophilic form of Thy-1 purified from human cerebrospinal fluid.

Thy-1 is a developmentally regulated cell surface glycoprotein in nervous tissue. An inositol-containing glycolipid structure is covalently attached to its carboxyl terminus, which anchors the protein to the cell membrane. In the present paper we report the characterization of a water-soluble form of Thy-1, purified from human cerebrospinal fluid (CSF). In contrast to the membrane-bound form of Thy-1 (M-Thy-1) isolated from human brain cerebral cortex, CSF-Thy-1 behaved like a completely hydrophilic glycoprotein, as analyzed by charge-shift electrophoresis in the presence of detergents and by liposome incorporation experiments. CSF-Thy-1 displayed a slightly higher apparent molecular weight in sodium dodecyl sulfate-polyacrylamide gel electrophoresis than M-Thy-1. Digestions with endoglycosidases demonstrated that this difference in size was correlated to different processing of the three N-linked oligosaccharides, and the mobilities of the deglycosylated molecules were indistinguishable in sodium dodecyl sulfate gels. A Pronase-resistant carboxyl-terminal fragment was isolated from the CSF-Thy-1 after trypsin digestion and compared with the corresponding structure of M-Thy-1, obtained by treatment either with bacterial phosphatidylinositol-specific phospholipase C or with human serum (as a source of phosphatidylinositol-specific phospholipase D). The major fragment from CSF-Thy-1 behaved identically, with respect to size and charge, to the carboxyl-terminal fragment from M-Thy-1 solubilized by phospholipase D. These findings suggest an in vivo release of phosphatidylinositol-anchored Thy-1 glycoprotein from brain cells by the action of an endogenous phospholipase D.

Antigens, Surface↗