Biomedical subjects

H Barth

Publications and source records attributed to H Barth.

At least 73 records · Page 4Linked to original sources

PubMed1998

Bolus Administration of Saruplase in Europe (BASE), a Pilot Study in Patients with Acute Myocardial Infarction.

To study the safety and efficacy of the thrombolytic agent saruplase as a bolus, the angiographic and clinical outcomes of three bolus regimens were investigated in a pilot study conducted in 192 patients with an acute myocardial infarction and were compared with the standard regimen. Fifty-two patients received a double bolus of 40 mg and 40 mg after 30 minutes, 51 patients a bolus of 80 mg, and 36 patients a bolus of 60 mg. Fifty-three patients received the standard regimen (a bolus of 20 mg and 60 mg IV infusion over 1 hour). At 60 minutes TIMI 2 and 3 flow were, respectively, 9.6% and 61.5% with the 40/40-mg bolus, 15.7% and 51.0% with the 80-mg bolus, 16.7% and 30.6% with the 60-mg bolus, and 7.5% and 54.7% with the standard 20/60-mg infusion. At 90 minutes TIMI 2 and 3 flow improved to 9.6% and 73.1%, 15.7% and 56.9%, 13.9% and 36.1%, and 5.7% and 71.7%, respectively. The primary endpoint, persistent patency (TIMI 2 + 3) at 24-45 hours, was seen in 69.2%, 64.7%, 44.4%, and 67.9% of patients who had no rescue PTCA, respectively. Inclusion in the 60-mg bolus group was prematurely stopped because of their low patency rates. The 40/40-mg bolus group had the highest mortality rate (13.5%), whereas the 60-mg bolus group had no deaths. Other adverse event rates were similar in the four groups. This clinical outcome is highly influenced by rescue PTCA of patients with insufficient TIMI flow. This pilot study indicates that in patients with an acute myocardial infarction, a double bolus of 40/40 mg resulted in the highest patency but also had the highest complication rate. The 80-mg single bolus is an attractive alternative for further evaluation because of its acceptable patency and event profile, and its easy form of administration.

Journal Article↗

PubMed1998

The N-terminal part of the enzyme component (C2I) of the binary Clostridium botulinum C2 toxin interacts with the binding component C2II and functions as a carrier system for a Rho ADP-ribosylating C3-like fusion toxin.

The binary actin-ADP-ribosylating Clostridium botulinum C2 toxin consists of the enzyme component C2I and the binding component C2II, which are separate proteins. The active component C2I enters cells through C2II by receptor-mediated endocytosis and membrane translocation. The N-terminal part of C2I (C2IN), which consists of 225 amino acid residues but lacks ADP-ribosyltransferase activity, was identified as the C2II contact site. A fusion protein (C2IN-C3) of C2IN and the full-length C3-like ADP-ribosyltransferase from Clostridium limosum was constructed. The fusion protein C2IN-C3 ADP-ribosylated Rho but not actin in CHO cell lysates. Together with C2II, C2IN-C3 induced complete rounding up of CHO and HeLa cells after incubation for 3 h. No cell rounding was observed without C2II or with the original C3-like transferase from C. limosum. The data indicate that the N-terminal 225 amino acid residues of C2I are sufficient to cause the cellular uptake of C. limosum transferase via the binding component of C2II, thereby increasing the cytotoxicity of the C3-like exoenzyme several hundred-fold.

ADP Ribose Transferases↗

PubMed1998

Intracranial cavernomas: indications for and results of surgery.

Between April 1991 and April 1997, 46 patients were treated in our department presenting with intracranial cavernomas. Initial symptoms were focal seizures, bleeding episodes, and/or headaches. Mean age was 41 year (range 9 to 68 years). There were 24 female and 22 male patients. Computed tomography and magnetic resonance imaging were performed in order to establish the diagnosis, angiography was only indicated when the hemorrhaged area was so close to the subarachnoid space in the vicinity of the basal cisterns that an aneurysm had to be ruled out. Aggressive indication for surgery also in brainstem cavernomas was based on the natural history of the lesion, since the majority of patients presenting with intracranial bleeding had suffered several (up to six) episodes of previous hemorrhages. Patients' clinical status upon admission and accessibility of the cavernoma were taken into account for planning the operation. The operative planning and approach were greatly facilitated by using a neuronavigational device and intraoperative electrophysiological monitoring particularly in cavernomas located in the brainstem, thalamus, and medulla oblongata. Surgical removal of the lesions resulted in a new permanent neurological deficit only in two patients (4%). These data show that patients benefit from modern neurosurgical techniques in contrast to conservative approach in this disease of rather prolonged natural course.

Adolescent↗

PubMed1998

Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 2nd communication: drops with ethanol.

The pharmacokinetics and the absolute bioavailability of tramadol hydrochloride (CAS 36282-47-0) after oral administration of Tramal drops (with ethanol) were determined in a balanced cross-over study in 8 (4 male and 4 female) volunteers in comparison with the intravenous injection. Each fasting volunteer received two single doses of 100 mg tramadol-HCl, one by oral (1 ml of drops) and one by intravenous route (2 ml of a solution for injection). The formulations were administered in the morning; the washout period was one week. Serum and urine concentrations of tramadol-HCl were determined by gas chromatography-mass spectrometry and gas chromatography, respectively, and the pharmacokinetic evaluation was carried out model-dependently. Only the extent of bioavailability and the renal clearance were calculated model-independently. The extent of the absolute bioavailability (F) of tramadol after oral administration of the drops, based on AUC data, was 66.3% (point estimate; n = 8) with a 95% confidence interval of 58.1-75.6% (ANOVAlog). The areas under the serum concentration curves of tramadol-HCl calculated by curve fitting (AUC), which agreed very well with the model-independently determined areas (AUC), were 2390 +/- 712 h.ng/ml (p.o.) and 3490 +/- 510 h.ng/ml (i.v.) (mean +/- SD; n = 8). After oral administration the means of the serum concentration peaks were 308 +/- 89 ng/ml (cmax) and 1.20 +/- 0.39 h (tmax), the half-life of absorption was 0.34 +/- 0.18 h (t1/2,ka) and the lag time 0.23 +/- 0.01 h (t0). The biological half-life in the terminal phase (t1/2,beta) was 5.5 +/- 0.9 h and agreed well with the value of 5.2 +/- 0.8 h determined after i.v. injection. There were large differences between the volunteers in the distribution rate. For the slower distribution half-life (t1/2,alpha) mean values of 1.2 +/- 0.7 h (p.o.; n = 6) and 1.9 +/- 0.7 h (i.v.; n = 6) were obtained. The values determined after i.v. injection for the total distribution volume and the total and renal clearance were 216 +/- 21 l (Vd,beta), 487 +/- 71 ml/min (Cltot) and 77 +/- 20 ml/min (Clren), respectively. These results show that after administration of the drops (with ethanol) the active ingredient tramadol is rapidly absorbed and that the extent of the absolute bioavailability is about the same as after oral administration of tramadol capsules.

Administration, Oral↗

PubMed1998

Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 3rd Communication: suppositories.

The pharmacokinetics and the absolute bioavailability of tramadol hydrochloride (CAS 36282-47-0) after rectal administration of tramadol suppositories (Tramal) were determined in a balanced crossover study in 10 female volunteers in comparison with the intravenous injection. Each fasting volunteer received two single doses of 100 mg tramadol-HCl, one rectally (1 suppository) and one intravenously (2 ml of a solution for injection). The formulations were administered in the morning, the washout period was one week. Serum concentrations of tramadol-HCl were determined by gas chromatography-mass spectrometry and the pharmacokinetic evaluation was carried out model-dependently. Only the extent of bioavailability was calculated model-independently. The extent of the absolute bioavailability (F) of tramadol in the suppositories, based on AUC data, was 77.0% (point estimate; n = 10) with a 95% confidence interval of 70.8-83.6% (ANOVAlog). The areas under the serum concentration curves of tramadol-HCl calculated by curve fitting (AUC), which agreed very well with the model-independently determined areas (AUC), were 2933 +/- 304 h.ng/ml (rectal) and 3775 +/- 446 h.ng/ml (i.v.) [mean +/- SD; n = 10]. Optimal curve fitting of the serum concentration data after rectal administration presupposed the existence of two absorption sites with different absorption rates and lag times. Under this premise the absorption half-lives were t1/2,ka;1 = 1.7 h (median; range: 1.1-3.1 h) and t1/2,ka;2 = 0.98 h (0.35-1.9 h), and the corresponding lag times were t0;1 = 0 h (0-0.37 h) and t0;2 = 0.66 h (0.31-3.5 h). The relative portion of the more rapidly absorbed quantity of tramadol varied between 9.2 and 50% (median: 28%). The maxima of the serum concentration curves were reached 2-6 h after rectal administration; the means of the individual maxima were 294 +/- 50 ng/ml (Cmax) and 3.3 +/- 1.3 h (tmax). There were large differences in the distribution rate between the volunteers. The means of the half-life of the slower distribution (t1/2, alpha) were 1.38 +/- 0.47 h (rectal; n = 10) and 1.78 +/- 0.63 h (i.v.; n = 7). In the terminal phase the biological half-life (t1/2, beta) was 5.7 +/- 1.0 h (rectal) and 5.7 +/- 0.9 h (i.v.), respectively. The values determined after i.v. injection for the total distribution volume and the total clearance were 216 +/- 231 (Vd, beta) and 447 +/- 56 ml/min (Cltot). The results show that after rectal administration of the tramadol suppositories the absorption of the active ingredient is rapid enough for therapeutic purposes and that the extent of the absolute bioavailability is higher than after oral administration of tramadol-HCl, probably due to a reduced first-pass metabolisation after rectal administration.

Adult↗

PubMed1997

Gene expression of the small GTP-binding proteins RhoA, RhoB, Rac1, and Cdc42 in adult rat brain.

GTPases of the Rho subfamily, i.e. Rho, Rac and Cdc42, are molecular switches in various signaling pathways. Best characterized are their functions in the regulation of the actin cytoskeleton. In neuronal cell lines they are involved in the mechanisms leading to synapse formation and plasticity. It is still unknown whether they have respective functions in the mammalian CNS. In this case, they should be present in the adult brain, especially in areas known for their synaptic remodeling. We have studied the expression of the Rho GTPases in adult rat brain with in situ hybridization and Western blot analysis. High amounts of RhoA, RhoB, Rac1 and Cdc42 mRNAs were detected in neurons of the hippocampus, i.e. in pyramidal cells of the CA1-CA4 regions as well as in granule cells of the dentate gyrus and in hilar cells. Also in cerebellum, Purkinje and granular cells expressed the four mRNAs. Strong gene expression was also found in brainstem, thalamus and neocortex. Using Western blot analysis, RhoA and Cdc42 proteins were detected in hippocampus, cerebellum, thalamus and neocortex. It is concluded that GTPases of the Rho family play a role in the regulation of cellular functions in the adult brain.

Animals↗

PubMed1997

Comparison of saruplase and alteplase in acute myocardial infarction. SESAM Study Group. The Study in Europe with Saruplase and Alteplase in Myocardial Infarction.

Four hundred seventy-three patients with acute myocardial infarction (AMI) were treated with either saruplase (80 mg/hour, n = 236) or alteplase (100 mg every 3 hours, n = 237). Comedication included heparin and acetylsalicylic acid. Angiography was performed at 45 and 60 minutes after the start of thrombolytic therapy. When flow was insufficient, angiography was repeated at 90 minutes. Coronary angioplasty was then performed if Thrombolysis In Myocardial Infarction (TIMI) trial 0 to 1 flow was seen. Control angiography was at 24 to 40 hours. Baseline characteristics were similar. Angiography showed comparable and remarkably high early patency rates (TIMI 2 or 3 flow) in both treatment groups: at 45 minutes, 74.6% versus 68.9% (p = 0.22); and at 60 minutes 79.9% versus 75.3% (p = 0.26). Patency rates at 90 minutes before additional interventions were also comparable (79.9% and 81.4%). Angiographic reocclusion rates were not significantly different: 1.2% versus 2.4% (p = 0.68). After rescue angioplasty, angiographic reocclusion rates of 22.0% and 15.0% were observed. Safety data were similar for both groups. Thus, (1) early patency rates were high for saruplase and alteplase treatment, (2) reocclusion rates for both drugs were remarkably low, and (3) complication rates were similar. Thus, saruplase seems to be as safe and effective as alteplase.

Aged↗

PubMed1997

Signal transduction through epidermal growth factor receptor is altered in HeLa monolayer cells during mitosis.

Epidermal growth factor (EGF)-induced signalling was studied separately in the mitosis and G2-phases of HeLa monolayer cells presynchronized (1) by amethopterin inhibition and thymidine release or (2) by nocodazole. For comparison, cells were treated with the phorbol ester phorbol 12-myristate 13-acetate (PMA). In contrast with the observed responses effected by PMA, which seem to be independent of cell cycle and synchronization conditions, those induced by EGF are greatly influenced by both criteria. Synchronization with nocodazole abolished the EGF-induced stimulation of phosphoinositide hydrolysis in G2 as well as in mitotic cells although tyrosine phosphorylation of the EGF receptor and phospholipase Cgamma1 could be shown to occur, especially in G2 cells. Synchronization with amethopterin/thymidine showed that, in contrast with G2 cells, mitotic cells were not able to react to EGF with an increase in phosphoinositide hydrolysis although a certain degree of EGF receptor dimerization and autophosphorylation as well as tyrosine phosphorylation of phospholipase Cgamma1 could still be shown to occur in mitosis. The results seem to indicate that the EGF pathway leading to a stimulation of phosphoinositide hydrolysis is attenuated at different levels and requires a cytoskeletal condition that is not present either after treatment (24 h) with nocodazole or during normal mitosis of a monolayer cell.

Antineoplastic Agents↗

PubMed1997

Microdeletion 22q11 in complex cardiovascular malformations.

Besides DiGeorge, velocardiofacial and conotruncal anomaly face syndromes, some of the isolated congenital heart diseases have also been associated with a chromosomal deletion in 22q11. These disease entities, which had originally been considered to have a different genetic background, are now included in the CATCH-22 microdeletion complex. CATCH 22 is an acronym for cardiac defect, abnormal facies, thymic hypoplasia or aplasia and T-cell deficiency, cleft palate, hypoparathyroidism, and hypocalcemia. In the present study, we focused on the complex cardiovascular defects (CCVD) and screened 40 patients for a microdeletion of 22q11 by fluorescence in situ hybridization using the D22S75 DNA probe and for associated CATCH features. The patients were from genetic counseling (n = 15) or fetopathology (n = 3) of the Clinical Genetics Department in Marburg and from the Pediatric Cardiology Department (n = 22) in Mainz. Monosomy 22q11 was detected in 9 cases (= 22.5%). Familial transmission with one mildly affected parent and one affected sib each was proven in two cases. The CCVDs comprised complex conotruncal defects such as tetralogy of Fallot, double outlet right ventricle, transposition of great arteries and truncus arteriosus communis, or anomalies of the derivatives of the branchial arch arteries in association with a ventricular septal defect, including one case of atresia of the ductus arteriosus with pulmonary artery aneurysm and resulting in fetal hydrops. All 13 patients with a deletion of 22q11 showed at least one additional CATCH symptom. Most consistently, facial dysmorphy was apparent (92%), while hypocalcemia, mostly at threshold values, was present in 62% and thymic hypoplasia including borderline low T-lymphocyte numbers was observed in 41%. None of the patients presented with a cleft palate. A high intrafamilial variability in expression was also evident with respect to the CCVD. Our findings indicate that seemingly isolated complex cardiovascular defects associated with a 22q11 microdeletion most probably do not represent a distinct subgroup within the CATCH-22 complex but are syndromal in nature with extracardiac features that are often overlooked.

Adolescent↗

PubMed1997

[Psammomamatoid ossifying fibroma of the frontal sinus with intracranial extension].

Case report of a 29-year-old woman with an psammomatoid ossifying fibroma of the left frontal sinus. Headache was the presenting clinical symptom. The tumor and its intracranial extension were identified by computed tomography and magnetic resonance tomography. Through a two-step combined neuro-rhinosurgical operation the tumor could be completely removed. Ossifying fibroma is a benign tumor mostly affecting the mandible and maxilla. A more aggressive approach may be more beneficial than expectant observation or curettage in the initial management of this benign neoplasm. Because of the unusual location of this rare entity the case history is published and differential diagnostic and therapeutical implications are discussed.

Adult↗

PubMed1996

Radiation with 1 Gy prevents the activation of the mitotic inducers mitosis-promoting factor (MPF) and cdc25-C in HeLa cells.

The mechanism of the transient G2 arrest induced by small doses of ionizing radiation involves the failure to activate the correctly formed pre-mitosis-promoting factor (MPF) complex of cyclin B and p34cdc2 by dephosphorylation at Tyr15 of the latter, as recent studies of other laboratories have indicated. Similar data were obtained with the G2 arrest-inducing agents epidermal growth factor and the phorbol ester 12-0- tetradecanoylphorbol-13-acetate (H. Barth and V. Kinzel, Exp. Cell Res., 212: 383-388, 1994, and H. Barth and V. Kinzel, J. Cell. Physiol., 162: 44-51, 1995). To differentiate the radiation consequences in synchronized HeLa cells from those of 12-0-tetradecanoylphorbol-13-acetate and epidermal growth factor, experiments with a very small dose (1 Gy) have been carried out in cells close to the G2-M border and, for comparison, in mitotic cells. We show that in addition to the failure of p34cdc2 dephosphorylation at Tyr15, radiation with 1 Gy also prevents the activation of the phosphatase cdc25-C, the enzyme catalyzing the MPF activation. In contrast, irradiation of mitotic cells with 1 Gy did not influence that fraction of either MPF or cdc25-C already activated. Moreover, the gain in MPM-2 antigenicity of cdc25-C, usually indicative of an activating phosphorylation, is shown to be prevented by 1 Gy. The data indicate that the initiation of the proposed autocatalytic loop between MPF and cdc25-C becomes interrupted by radiation, but they give no hint at which point.

CDC2 Protein Kinase↗

PubMed1996

Role of cdc25-C phosphatase in the immediate G2 delay induced by the exogenous factors epidermal growth factor and phorbolester.

Studies on the link between cellular signalling and cell cycle control at the G2 checkpoint have shown that, in HeLa cells, epidermal growth factor (EGF) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) rapidly inhibit the G2-M transition by preventing the key component of mitosis-promoting factor (MPF), p34cdc2, from expressing protein kinase activity. The kinase activity of active MPF is not inhibited; rather, the conversion of pre-MPF to MPF, i.e., the activating dephosphorylation of p34cdc2, at tyrosine is rapidly blocked (Barth and Kinzel, 1994, Exp. Cell Res. 212:383-388; 1995, J. Cell. Physiol., 162:44-51). The phosphatase responsible, cdc25-C, is activated by phosphorylation in mitotic cells starting at the G2-M transition in an autocatalytic loop with MPF (Hoffmann et al., 1993, EMBO J. 12:53-63). We now show that, concomitant with the prevention of MPF activation, EGF and TPA induced a reduction of the activity of cdc25-C in synchronized cultures. Furthermore, treatment of mitotic HeLa cells with TPA did not influence the kinase activity of MPF but caused a rapid decrease of the specific enzyme activity of cdc25-C, probably due to dephosphorylation of the enzyme, as indicated by reduced binding of monoclonal MPM-2 antibody specific for phosphoepitopes in M phase. Because of its inability to induce signalling during division, EGF failed to influence the activity of cdc25-C in mitotic cells. The scenario in cells late in G2 that are committed to enter mitosis may be as follows: In those cells where the signalling pathways responding to EGF as well as those responding to TPA are still open, cdc25-C is prevented by dephosphorylation from exceeding the threshold level of activity required to initiate the activation of and the autocatalytic feedback loop with p34cdc2 and to enter mitosis. Therefore, cdc25-C appears to represent part of an interface between cellular signalling and cell cycle control in G2 phase.

CDC2 Protein Kinase↗

PubMed1996

Pharmacokinetics and absolute bioavailability of lansoprazole.

OBJECTIVE: In a crossover study 12 healthy volunteers received lansoprazole 15 mg or 30 mg orally, or 15 mg intravenously in randomized order as a single dose. Blood samples were taken and plasma levels of lansoprazole were determined using an HPLC method. The volunteers were phenotyped for the debrisoquine/sparteine and mephenytoin polymorphisms. RESULTS: The total clearance was 517 ml.min-1, and the absolute bioavailability was 91% for the 30-mg and 81% for the 15-mg enteric-coated formulation. The elimination half-life was about 1 h. No correlation of the plasma levels to the sparteine metabolic ratio was found, and no correlation to the mephenytoin type could be established, since all volunteers of the mephenytoin type were extensive metabolizers. Although considerable variation, inter- and intraindividually, was observed, the increase in Cmax and AUC did not deviate from dose proportionality. The present galenic formulation ensures a high bioavailability after a single dose.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

[Intracerebral hemorrhage after systemic thrombolysis in patients with occlusion of the central retinal artery. Report of 2 cases].

Pharmacological thrombolysis is a valuable therapeutic modality for embolic arterial occlusion. Nevertheless, thorough evaluation of the indications is imperative to avoid serious complications. The most frequent complication is hemorrhage. Of these, the intracerebral hemorrhages are rare, but when they do occur they are an immediate threat to life they are accompanied by very severe complications, and they have an extremely poor prognosis. Within 58 months 361 patients were treated at our neurosurgical clinic with intracerebral hematomas. In 22 patients (6.1%) the hematoma developed as a complication of systemic thrombolysis. Two of these patients had been treated for occlusion of the central retinal artery. One patient died: the other survived but was severely disabled. The latter patient experienced no benefit from the thrombolysis as for as the underlying ophthalmologic disease was concerned. These worrying examples stress the necessity for careful evaluation of risk factors and the natural history of the underlying disease for which systemic thrombolysis is indicated. Local selective (or superselective) thrombolysis is preferable to the systemic procedure, provided that the indications are equally strictly observed and are less likely to lead to severe complications.

Aged↗

PubMed1996

[Perimesencephalic subarachnoid hemorrhage--an independent clinical picture of non-aneurysmatic subarachnoid hemorrhage with a benign course].

Two hundred seventy-three Patients with acute SAH were treated within the last 46 months (1.4.1991 to 31.1.1995). Diagnosis was made upon visible SAH on CT-scans or bloody spinal tap regardless of a negative CT-scan. These patients harbored 194 aneurysms, 25 AVM and cavernomas. Within the same time-period we treated 27 Patients without SAH but harboring vascular malformations (17 aneurysms, 10 AVM and cavernomas). In 30 patients (11%) no bleeding source was detectable. Fourteen of these patients (5.1%) had blood concentrated within the perimesencephalic cisterns on the CT-scans. On admission all of these 14 patients (8 men, 6 female, aged 30 to 63 years) were awake and without mentionable neurological deficit, equalling Hunt & Hess grade 1 (11 patients) and 2 (3 patients). Neither the initial nor control angiography revealed a vascular malformation as a bleeding source. MRI-scans performed for 11 patients did not reveal further etiological clues. During a follow-up interval of 3 to 48 months, none of these patients suffered a rebleeding. Vasospasm was not or only slightly present, no ischemia leading to neurological deficit. GOS reached 5 and Karnofsky-scale was 100 for all of these patients. We conclude that the perimesencephalic SAH is a homogeneous entity with a different natural course than the common aneurysmatic SAH. Probably leakage within the capillary or venous circulation causes this form of SAH with a benign clinical course. Further experience is required to determine whether control angiography is mandatory in these patents with a distinct CT appearance.

Adult↗

PubMed1996

[Primary traumatic midbrain syndrome--follow-up and prognosis of acute primary brain stem damage].

Within 27 months 122 patients with severe head injury were treated at our clinic. Of these patients twelve (9.8%) were categorized as having a primary brain stem lesion (9 male and 3 female, mean age 28.3 years (17 to 73 years). Their injuries were caused primarily by traffic accidents. Initial and follow-up CT ruled out mass lesions or other causes for transtentorial herniation, supporting the diagnosis of primary brain stem lesion. Respiratory insufficiency and control of vegetative function demanded artificial ventilation and analog-sedation for up to 32 days (mean 18 days) on our Intensive Care Unit. In all patients we performed initial and follow-up CT scans, ICP monitoring, evoked potentials (AEP, SSEP) and TCD. MRI was carried out in four patients. One patient died during the acute hospital phase, 7 were transferred in poor and four in good condition. During rehabilitation one patient died, two, one in a vegetative state and one in poor condition were transferred to a caring facility. Eight patients with a good or moderate recovery were dismissed home, subsequently regaining their prior social function. The primary traumatic brain stem lesion presents as a dramatic clinical picture. As shown in our series the prognosis is good independent of the duration of coma. The important prognostic factors were the primary neurological state according to the Gerstenbrand and Luecking classification, the degree of the brain stem lesion in CT scan and MRI, and normal evoked potentials, indicating a favourable outcome.

Adolescent↗

PubMed1995

Epidermal growth factor rapidly impairs activation of p34cdc2 protein kinase in HeLa cells at the G2-M boundary.

Epidermal growth factor (EGF) has been shown rapidly to inhibit the transition from G2 phase to mitosis: beyond this transition point the cells are refractory to EGF (Kinzel et al., 1990, Cancer Res., 50:7932-7936). Using synchronized HeLa cells, EGF has now been shown to induce an overall decrease of the histone H1 kinase activity of p34cdc2 after 20 min of treatment, a time course which correlates with the number of cells in metaphase. The kinase level of actively mitotic cells is not altered by EGF. Neither the amount of p34cdc2 protein present nor that of Cyclin B in influenced by EGF, and the formation of the p34cdc2/Cyclin B complex is also unaffected. The use of antiphosphotyrosine antibodies, however, showed that p34cdc2 from cultures treated with EGF was more intensely stained than that of control cells, indicating that EGF treatment prevents the tyrosine dephosphorylation which is required for expression of the protein kinase activity of the complex. Taken together, the results show that EGF in HeLa cells very rapidly prevents the p34cdc2/Cyclin B complex from expressing kinase activity at the G2-M boundary, which appears to be the cause for the inhibition in G2 phase.

Blotting, Western↗

PubMed1995

Saruplase in Myocardial Infarction.

Saruplase is an unglucosylated single-chain recombinant urokinase-type plasminogen activator. Dose finding studies in patients with acute myocardial infarction indicated that a dose of 80 mg of saruplase, given as a bolus of 20 mg and iv infusion of 60 mg in one hour, led to excellent patency figures.Saruplase is most effective when combined with a bolus of 5000 IU heparin followed by an iv heparin infusion for at least 24 hours.When saruplase is compared to other thrombolytic agents (streptokinase, alteplase, urokinase), it becomes apparent that its profile is excellent. Early patency rates are at least comparable to alteplase. Further reocclusion rates of saruplase after one day are lower than those of streptokinase and alteplase. Patency rates 24-72 hours after start of medication are comparable between saruplase and urokinase.The large database in over 6000 patients shows that saruplase, in comparison to the other thrombolytic agents, is safe. Its bleeding complication rate is significantly lower than streptokinase, and a trend to lower in-hospital mortality is observed when compared to urokinase.Summarizing, when comparing to the presently available thrombolytic agents, saruplase is a fast acting, effective and safe thrombolytic agent.

Journal Article↗