bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Cognitive Function in Asymptomatic HIV-Positive Subjects
Authors: Grassi Maria Pia , Perin Cecilia , Borella Monica , Mangoni Alfonso
Published: April 2003

This retrospective study aims to assess cognitive involvement in pre-AIDS, not drug abuser subjects and to determine whether CD4 status or disease stage best correlates with cognitive changes that may portend development of ADC. 328 cases were analyzed. No differences in psychometric performance in relation to CDC stage were found. Instead, patients with CD4 < 200/μl performed worse overall, with a statistically significant difference for Digit Symbol, Corsi Test, Block Design and HIVDA Scale. Even if cognitive decline is not evident in the early phase of HIV infection, CD4 count seems the more sensitive early indicator of cognitive changes adequately pointed out by the HIVDA Scale, which could be considered a useful screening tool for cognitive deficit.
Seizures and Epilepsy following Strokes: Recurrence Factors
Authors: Berges Sophie , Moulin Thierry , Berger Eric , Tatu Laurent , Sablot Denis , Challier Bruno , Rumbach Lucien
Published: April 2003

Background and Purpose: Though there have been many reports on poststroke seizures, there is still much we do not know about them. Using a large cohort of stroke patients we analyzed the characteristics of the seizure(s) and the rate and factors involved in seizure recurrence. Methods: Out of the 3,205 patients admitted for a first-ever stroke to our department between 1984 and 1994, we retrospectively studied the data of all patients with a first-ever seizure and analyzed their evolution. Two types of seizure(s) were defined: ‘early-onset’ seizures (occurring within the 14 days following the stroke) and ‘late-onset’ ones (after the 14th day). Results: 159 patients were included in the study, i.e. 4.96%. There were 116 ischemic strokes and 43 primary hematomas. Cortical involvement was found in 87% of the patients. Early-onset seizures occurred in 57 patients and late-onset ones in 102 patients, 76% of which were observed within 2 years. Follow-up was performed in 135 patients with a mean follow-up period of 47 months; 68 of them presented a seizure recurrence. A 2nd seizure occurred more often in the patients with late-onset seizures (p < 0.01); recurrence was either single (24 patients) or multiple (44 patients). Univariate analysis demonstrated 3 factors for multiple recurrences: hemorrhagic component, low Rankin scale after the initial seizure and occipital involvement. Multivariate analysis determined 2 factors: occipital involvement and late onset of the 1st seizure as a predictive model of multiple recurrences. Conclusions: This study confirms that poststroke seizures are frequent and must be divided into 2 types: early-onset (≤14 days) and late-onset seizures. It demonstrates that a significantly lower rate of patients with early-onset seizures develop another seizure, i.e. epilepsy, than do patients with late-onset seizures. Other factors are involved in recurrence suggesting that poststroke epilepsy probably occurs in a chronically injured brain. The problem of treatment remain unanswered.
Pure Homonymous Hemianopia due to Anterior Choroidal Artery Territory Infarction
Authors: Han Sang-Won , Sohn Young H. , Lee Phil-Hyu , Suh Bum-Chun , Choi Il-Saing
Published: April 2003

The most consistently observed neurological deficits in the anterior choroidal artery (AChA) territory infarction are pure motor or sensorimotor syndromes. Visual field defects and higher cortical dysfunction are occasionally accompanied, but pure homonymous hemianopia without motor and sensory symptom has never been reported yet. We present 2 patients with pure homonymous hemianopia, whose MRI disclosed cerebral infarction in the well-known territory of the AChA. In most patients with ischemic stroke, pure homonymous hemianopia indicates infarction in the posterior circulation, particularly in the posterior cerebral artery territory. However, the present cases provide evidence that it can also be caused by infarction in the anterior circulation, i.e. the AChA.
Proximal Myotonic Myopathy:Clinical, Electrophysiological andPathological Findings in a Family1
Authors: Kohler A. , Burkhard P. , Hefft S. , Bottani A. , Pizzolato G.P. , Magistris M.R.
Published: April 2003

Proximal myotonic myopathy (PROMM) is an autosomal dominant muscle disorder characterized by proximal weakness, myotonia, muscle pain and cataract. It resembles Steinert myotonic dystrophy (MD), but weakness is proximal, without facial muscle involvement, and the chromosome 19 CTG trinucleotide repeat expansion characteristic of MD is not present. We describe a further family with PROMM. Affected members complained of weakness of lower limbs or of myotonia. EMG revealed diffuse myotonic discharges. Muscle histology showed dystrophic abnormalities. The PROMM phenotype varies, even in the same pedigree, and may mimic MD or limb-girdle muscle dystrophy. EMG is particularly useful, since it may disclose myotonic discharges even in the absence of overt myotonia. Thus far it is not known whether PROMM is a single entity, or if it represents a heterogeneous group of disorders. This question will probably soon be settled through genetic analysis.
Therapies in Muscular Dystrophy: Current Concepts and Future Prospects
Authors: Urtizberea J. Andoni
Published: April 2003

In the fast moving field of muscular dystrophy, therapeutic matters are now high on the agenda. Despite little progress made in the understanding of the exact pathogenesis, hopes have been raised with the advent of molecular medicine applied to such disorders. A constellation of techniques or therapeutic solutions are now available, but very few have reached the clinical stage. Gene therapy, cell therapy and pharmacological therapy look more promising, but their clinical application may still take years. We review the various alternatives and suggest that some of them might be used in combination.
Angiotensin-Converting Enzyme Gene Deletion Polymorphism Determines an Increase in Frequency of Migraine Attacks in Patients Suffering from Migraine without Aura
Authors: Paterna Salvatore , Di Pasquale Pietro , D’Angelo Alessandra , Seidita Gregorio , Tuttolomondo Antonino , Cardinale Antonietta , Maniscalchi Tiziana , Follone Giuseppe , Giubilato Alfonso , Tarantello Marco , Licata Giuseppe
Published: April 2003

Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura. In 302 patients suffering from migraine without aura (at least for 1 year), with no history of cardiovascular diseases and major risk factors for ischemic events, the genotypes of the ACE gene, plasma ACE activity, and the frequency (weekly) and duration of migraine attacks were evaluated. No drugs were given before (4 weeks) and during the study. The same evaluations were performed in 201 subjects without migraine. The molecular biologist and the physician evaluating the patient data were blinded to the clinical history and ACE-DD gene determination. Genotypes were determined by polymerase chain reaction amplification. Plasma ACE activity was performed by the HPLC method. The groups were similar for sex, age and smoking habit (migraines: 302 patients (200 F/102 M), mean age 37.8 ± 8.2 years; control: 201 subjects (127 F/74 M), mean age 37.5 ± 9.3 years). Patients with migraine without aura showed higher incidence of the ACE-DD gene (48.34%) than control subjects (37.32%), p < 0.05. The frequency of migraine (average attacks per week) was higher in patients with DD (2.11 ± 1.9) than in patients with ID (1.54 ± 1.44), p < 0.05. No difference in duration of migraine attacks (hours per week) was observed. Plasma ACE activity was increased in patients with the ACE-DD gene. Our data suggest that ACE-DD gene polymorphism could have an important role in determining migraine attacks and the frequency of these attacks. Further data are needed through further studies, especially on the biomolecular level.
Age-Dependent Decline in the Apolipoprotein E Level in Cerebrospinal Fluid from Control Subjects and Its Increase in Cerebrospinal Fluid from Patients with Alzheimer’s Disease
Authors: Fukuyama Ryuichi , Mizuno Toshiki , Mori Satoru , Yanagisawa Katsuhiko , Nakajima Kenji , Fushiki Shinji
Published: April 2003

In order to address the significance of apolipoprotein E (apoE) in the pathogenesis as well as the clinical diagnosis of Alzheimer’s disease (AD), we measured its level in cerebrospinal fluid (CSF) from randomly selected Japanese control subjects at various ages (n = 36), which included 14 age-matched controls, and from AD patients including early-onset (n = 11, EOAD) and late-onset (n = 14, LOAD) cases. The CSF apoE level in controls linearly decreased during aging to over 80 years (r2 = 0.323, p < 0.0001). The CSF apoE level in AD patients was 31.9% elevated compared to the age-matched controls (n = 14, p < 0.05) and linearly increased with a decrement of the patients’ Mini Mental State Examination scores. Moreover, the CSF apoE level of EOAD patients (n = 11) was higher than that of LOAD patients (n = 14, p < 0.05), whose APOE ε4 allele frequency was significantly higher than that of controls (χ2 = 7.16, p < 0.03). Two-dimensional gel electrophoretic analysis of the heparin-Mn2+-precipitable lipoprotein fraction in CSFs showed that the ratio between the level of CSF apoA-I and that of CSF apoE of controls was significantly higher than those of all AD and LOAD subjects (p < 0.01, p < 0.05), while the CSF apoA-I-to-apoE ratios of the two AD groups were not significantly different. These results suggest that overproduction of apoE protein may be a consequence of astroglial response to neurodegeneration in AD and that the determination of CSF apoliprotein levels serves as a clinical marker for monitoring the progression of AD.
Effect of Tolcapone on the Haemodynamic Effects and Tolerability of Desipramine
Authors: Jorga K.M. , Fotteler B. , Modi M. , Rabbia M.
Published: April 2003

Background and Purpose: To determine the changes in haemodynamics, tolerability and pharmacokinetics that may occur when a combination of tolcapone and levodopa/carbidopa are given with desipramine. Methods: In a crossover study, 22 healthy subjects received desipramine during two 13-day treatment periods (25 mg t.i.d. for 3 days and 50 mg t.i.d. for 10 days), with a washout period of 10–15 days. Subjects received levodopa/carbidopa (100 mg/25 mg t.i.d. for 5 days, days 9–13) and concomitant, double-blind, randomized treatment with either tolcapone (200 mg t.i.d.) or placebo. Results: No significant pharmacodynamic and pharmacokinetic interactions occurred between tolcapone and desipramine. Adverse events were predictable based on the known effects of the individual drugs. Conclusions: Tolcapone can be combined with levodopa/carbidopa and desipramine in patients with Parkinson’s disease.
Prevalence of Arylsulfatase A Pseudodeficiency Allele in Metachromatic Leukodystrophy Patients from Poland
Authors: Ługowska Agnieszka , Czartoryska Barbara , Tylki-Szymańska Anna , Bisko Mariola , Zimowski Janusz G. , Berger Johannes , Molzer Brunhilde
Published: April 2003

Arylsulfatase A (ASA) pseudodeficiency (PD) allele was searched for in 22 patients originating from Poland and suffering from different types of metachromatic leukodystrophy (MLD). Four of them carried the PD allele in a heterozygous state. The prevalence of the PD allele among investigated MLD patients was revealed to be 9%, while the frequency of the PD allele in healthy controls was estimated at 6–7%. One of the examined MLD patients was additionally a carrier of an isolated mutation leading to the loss of the N-glycosylation site. The question arises whether and how MLD mutations create a convenient milieu for PD mutations to occur (or inversely).
Differential Device Performances for Hepatic Arterial Chemotherapy: A Technical Report on Totally Implantable Pumps and Ports for Both Continuous and Bolus Infusion
Authors: Civalleri D. , De Cian F. , Pellicci R. , Balletto Nadia , Simoni G. , Cosimelli M. , Mondini G. , Bignami Paola , Cagol P.P.
Published: April 2003

Performances of totally implantable infusion systems were analyzed in patients with colorectal liver metastases undergoing intra-arterial treatment. It consisted of 14-day continuous infusion of 5-fluor-2′deoxyuridine with pumps (pump14, 44 patients) or ports fed by external pumps (port14, 34 patients), or bolus infusion of cisplatin (port21, 57 patients) or epirubicin (port7, 22 patients) every 3rd week and weekly, respectively. Toxicity and disease progression were the most common causes of treatment interruption. System failure occurred in 2 pump14, 9 port14, 6 port21 and 2 port7 cases. Pocket problems were most frequent in the pump14 group (30%), whereas catheter- and infusion-related problems were mostly observed in the port14 group (109%). The devices were still functional after 12 months in 92% of pump14, 24% of port14, 65% of port21 and in 78% of port7 patients. Although implantable ports allow adequate infusion periods, in most cases they appear especially suitable for bolus infusions.
Blood Flow in Rat Gastrocnemius Muscle and Achilles Tendon after Achilles Tenotomy
Authors: Józsa L. , Kannus P. , Järvinen T.A.H. , Balint J. , Järvinen M.
Published: April 2003

The effect of Achilles tenotomy on resting blood flow of rat gastrocnemius muscle and Achilles tendon was studied by radioactive microspheres. Tenotomy produced an immediate, marked decrease in both intramuscular and intratendinous blood flow and it remained significantly lowered at both sites till the end of the observation period, i.e., day 18 after tenotomy. The decrease in the resting blood flow was more rapid and pronounced in the Achilles tendon than in the gastrocnemius muscle. Although the blood flow of the Achilles tendon started to recover after the 4th postoperative day, it was still 33% (statistically not significant) lower than that in the controls 18 days after tenotomy. In the gastrocnemius muscle, the 18-day deficit was 38% (p < 0.001), respectively. The results indicate that after division of a rat Achilles tendon the resting blood flow to the gastrocnemius muscle and Achilles tendon is not adequately restored, remaining at a significantly lowered level even 18 days after tenotomy.
Influence of Intermittent Ischemia on Thioacetamide-Induced Rat Liver Cirrhosis
Authors: Matsutomo H. , Hirose H. , Senga S. , Fukuchi T. , Imai N. , Hayashi M. , Katagiri Y. , Onitsuka A.
Published: April 2003

We studied the influence of intermittent ischemic injury on thioacetamide-induced liver cirrhosis in rats. Wistar rats were divided into group A, intermittent ischemic injury to liver cirrhosis, and group B, continuous ischemic injury to liver cirrhosis. Total ischemic time was 60 min in both groups. In group A, ischemic injury consisted of a repetition 4 times of 15 min ischemia and 5 min reperfusion. The ATP level of the liver was measured before ischemia, before reperfusion, and 60 min after reperfusion. Bile was collected to determine bile flow rate. The ATP level in the liver tissue 60 min after reperfusion was significantly (p < 0.05) higher in group A than in group B. The ATP level immediately before reperfusion was also significantly (p < 0.05) higher in group A than in group B. The survival rate 1 week after ischemic injury and bile flow rate 60 min after reperfusion were significantly (p < 0.01) higher in group A compared with those in group B. The energy level was much higher in intermittent ischemic injury than in continuous ischemic injury immediately before reperfusion and after reperfusion. Survival rate and bile flow rate were higher in intermittent ischemic injury than in continuous ischemic injury. Therefore it suggests that the viability of the liver was maintained better in intermittent ischemic injury than in continuous ischemic injury.
Serum β-Endorphin Levels in Morbidly Obese Patients: The Effect of Vertical Banded Gastroplasty
Authors: Karayiannakis A.J. , Zbar A. , Makri G.G. , Syrigos K. , Athanasiadis L. , Alexiou D. , Bastounis E.A.
Published: April 2003

The associations between serum β-endorphin levels and clinical and metabolic variables as well as β-endorphin changes after surgically induced weight loss were investigated in 43 morbidly obese patients. A significant positive correlation between β-endorphin and body weight, degree of body weight increase and ACTH was found preoperatively. Only body weight was independently associated with β-endorphin levels. Twelve months following vertical banded gastroplasty, there was an extensive weight loss in all patients and improvement in their metabolic profile. A significant reduction in β-endorphin levels which was proportional to the extent of weight loss was also observed.
Optimization of the Kinetics of Cooling of Kidneys: A Pig Model
Authors: Savioz D. , Jeanjacquot A. , Savioz M. , Ludwig Corinna , Chilcott M. , Bolle J.F. , Graf J.D. , Nastasi A. , Morel Ph.
Published: April 2003

We determined the kinetics of cooling in multiple organ procurement for the kidney in a pig model. A biometric analysis by regression enables us to define the factors which influence the rate of temperature decrease: weight of the donor, average rate of perfusion and difference of temperature between the rectal temperature and the temperature of the perfusion solution at initiation of cooling. The description of the temperature as a function of time follows an exponential model of the type T(t) = T₀·edt where d is the rate of decrease. The rate of decrease varies according to the above factors. The cellular viability ratio (CVR), was correlated to the rate of cooling. The mean CVR was 91% (SD 4.95) when the rate of cooling was more than 1°C/min. This was compared to 75% (SD 11.17) when the rate was less than 1°C/min (p = 0.023). Our experience leads us to believe that the average cooling rate is frequently too low (<1°C/min). This model can be used to predict and control the kinetics of cooling and may help to define the best way of cooling for future xenotransplantation.
Drug Choices for Intravenous and Spinal Analgesia
Authors: Fitzgibbon D.R. , Ready L.B.
Published: April 2003

Opioids remain at the center of most postoperative pain control therapies. The choice between full agonist opioids should be determined by the time for a given dose to produce its maximum effect (i.e., latency to peak effect), and the duration of action. There is little to choose between different opioids administered by patient-controlled analgesia. Parenterally-administered NSAIDs (e.g., ketorolac) contribute significantly to analgesia and reduce opioid requirements. Morphine may be the opioid of choice for epidural administration. The combination of epidural opioids and local anesthetics provides synergistic analgesia and appears to provide superior analgesia with activity. Several nonopioid receptor agonists are under investigation as neuraxial analgesics.
Patient-Controlled Analgesia: An Efficient Therapeutic Tool in the Postoperative Setting
Authors: Lehmann K.A.
Published: April 2003

Patient-controlled analgesia (PCA) is one of the newer techniques for pain management. It was developed in reaction to the large number of unsatisfied postoperative patients suffering from moderate to severe pain despite the availability of potent analgesic drugs. With PCA, patients are allowed to self-administer small analgesic doses into a running intravenous infusion, intramuscularly, subcutaneously or even into the spinal space. Clinical experience soon demonstrated that individual variability in pain intensity and analgesic needs was extremely large. Psychological factors seem to be as important as the surgical trauma. Opioid consumption is usually higher than with conventional regimens, but without serious side effects. Although patients generally prefer self-control, pain relief is not necessarily better than with well-conducted conventional techniques. In addition to routine clinical pain management, PCA has proven its importance in research, e.g. for pain measurement, to determine predictors of postoperative pain, to evaluate drug interactions and the concept of pre-emptive analgesia, or for pharmacokinetic designs. PCA has been extremely important in order to change the mind of physicians and nursing staff with respect to individual pain management strategies.
Pancreatic Growth after Pancreatico-Biliary Diversion Does Not Increase the Capacity to Secrete Amylase
Authors: Axelson J. , Jansen C. , Sternby B. , Björkman A. , Rehfeld J.F. , Ihse I.
Published: April 2003

Background/Aim: Cholecystokinin (CCK) stimulates secretion and evokes a hyperplastic response in the rat pancreas. The aims of this study were to measure the effect of chronic hyperCCKemia induced by pancreatico-biliary diversion (PBD) on pancreatic enzyme concentrations, on amylase secretion by dispersed acinar cells, and on the CCK-stimulated secretion of pancreatic juice in PBD-operated rats. Material and Methods: Forty-five Sprague-Dawley male rats had either PBD or sham operation 4 weeks before sacrifice or additional experiments. In the first study, 25 rats (13 PBD and 12 sham-operated rats) were either freely fed or fasted overnight before sacrifice. The pancreas was dissected out, weighed and analyzed. In the second study, the rats (6 PBD and 7 sham-operated rats) were fasted overnight before pancreatic acini were prepared. Secretion of amylase during stimulation of acini with CCK-8S and carbachol was measured. In the third study (5 sham-operated and 4 PBD rats), the rats were fasted overnight before basal and CCK-stimulated secretion was measured in vivo. Results: PBD-operated rats showed a threefold increase in pancreatic wet weight with increased contents of DNA, protein and water. The concentration of pancreatic amylase was 7–12% of that found in control animals. The concentrations of trypsin and lipase were also lowered. Stimulation of dispersed pancreatic acini with CCK-8S or carbachol resulted in secretion of amylase to a similar extent in PBD and sham-operated rats. There was no difference in the secretion of pancreatic juice in response to CCK, but although the output of amylase from PBD-operated rats increased with CCK, it remained at a low level throughout the study period. Conclusion: PBD evoked hyperplastic changes in the rat pancreas and decreased the concentrations of amylase, trypsin and lipase. However, the capacity of acinar cells to secrete amylase remained intact. The stimulated pancreatic secretion was not changed in volume, but the output of amylase was low in PBD-operated rats. The findings are consistent with the idea that the enlargement of the pancreas following PBD does not improve the secretory capacity.
Isolated Lung Perfusion with Melphalan Prolongs Survival in a Rat Model of Metastatic Pulmonary Adenocarcinoma
Authors: Hendriks J.M.H. , van Schil P.E.Y. , van Oosterom A.A.T. , Kuppen P.J.K. , van Marck E. , Eyskens E.
Published: April 2003

Introduction: Survival after isolated lung perfusion (ILuP) with melphalan was tested in a model of unilateral pulmonary adenocarcinoma. Methods: On day 0, rats were randomized into four groups: Group 1 (n = 9) reveived tumor cells intravenously for induction of bilateral lung metastases, whereas groups 2–4 (n = 21) underwent a 10-min occlusion of the right pulmonary artery during tumor cell injection for induction of unilateral left lung metastases. On day 7, groups 1 and 2 received no treatment. Group 3 underwent left ILuP with melphalan (2.0 mg/kg) while group 4 received melphalan intravenously (0.5 mg/kg). The end point of the study was death from metastatic disease. Results: Median survival of ILuP-treated animals (81 ± 12 days) was significantly longer compared to group 1 (18 ± 1 days; p = 0.0001), group 2 (28 ± 3 days; p = 0.0002) and group 4 (37 ± 6; p = 0.0004). Conclusions: ILuP with melphalan prolongs survival in the treatment of experimental metastatic pulmonary carcinoma.
Porcine Living Liver Transplantation Using a Vascular Prosthesis to Replace the Intrahepatic Vena cava
Authors: Nardo B. , Catena F. , Turi Paola , De Vincentis F. , Simoncini Mara , Faenza A. , Bellusci R. , Mazziotti A. , Cavallari A.
Published: April 2003

Background: This study aimed to determine whether the porcine model could be adapted to accommodate living donor liver transplantation (LLT). Because the pig hepatic anatomy precludes a standard approach, a study was designed to evaluate the results using a segment of vascular prosthesis to replace the intrahepatic portion of the inferior vena cava (IVC) with establishment of hepatic venous drainage into the graft. Methods: A total of 10 LLT were performed using 20 pigs. After left hepatectomy, the intrahepatic IVC was replaced with a modified aorto-iliac prosthesis, anastomosing the proximal (aortic limb) to the infradiaphragmatic IVC, one distal iliac limb to infrahepatic IVC and the other (after shortening) to establish hepatic venous drainage after transplant. Conventional venous bypass was used, and no immunosuppressives were administered. Results: All donors survived the 10-day posthepatectomy observation period. Eight of the 10 transplanted pigs survived at least 2 days (mean 7.6 days; range 3–13 days). No evidence of caval graft thrombosis was observed. Conclusions: Replacement of the recipient intrahepatic IVC by a vascular prosthesis allows to overcome the major technical obstacle which has limited the use of pigs in LLT.
Inhibitory Effect of a Gastrin Receptor Antagonist, CR2945, on 1,2-Dimethylhydrazine-Induced Colorectal Cancer in Mice
Authors: Fontana Maria Grazia , Donato F. , Villanacci V. , Ghirardi M. , Moneghini D. , Di Betta E. , Salerni B.
Published: April 2003

This study tested the effect of a new gastrin receptor antagonist, CR2945, on colorectal cancer induced by 1,2-dimethylhydrazine (DMH) in mice. 75 CD1 male mice were divided into 3 groups: group 1 received 1 weekly injection of 20 mg/kg of DMH and 2 daily intraperitoneal injections of 0.5 ml of NaCl 0.9% solution for 5 weeks; groups 2 and 3 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/kg for 5 weeks. The animals were sacrificed 25 and 38 weeks after the first injection. No tumours were found at the 25th week. A lower cancer frequency (4%) was observed in treated animals compared to controls (37.4%) at the 38th week (p = 0.002). These data show that CR2945 could prevent chemically induced colon cancer development in mice.
Isolated Hyperthermic Liver Perfusion with High Dose Tumor Necrosis Factor Alpha in Pigs: An Experimental Study in Preparation of Clinical Use
Authors: Lang H. , Thyen A. , Nadalin S. , Frerker M. , Moreno L. , Flemming P. , Martin M. , Oldhafer K.J. , Raab R.
Published: April 2003

Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2°C. In two study groups B and C (n = 9 pigs each) 50 μg recombinant human tumor necrosis factor-α (rhTNFα) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFα. Before reperfusion the livers were washed out with Ringer’s solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFα concentrations were significantly higher in group B with 68 and 61 ng/ml compared to 14.5 and 14.9 ng/ml in group C (p < 0.05). Mean systemic porcine TNFα concentration was significantly higher in group B (217 pg/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). Survival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dying due to severe cardiopulmonary failure within 12 h after operation. In surviving pigs of group A and C only mild and transient hepatotoxicity was registered. The presented study underlines the feasibility of high dose rhTNFα application in an isolated hyperthermic liver perfusion system. Washout of the liver with a protein solution before reperfusion reduces systemic TNFα levels as well as associated lethal cardiocirculatory and hepatotoxic side effects.
Computer-Assisted ex vivo, Normothermic Small Bowel Perfusion
Authors: Stangl M.J. , Krapp J. , Theodorou D. , Eder M. , Hammer C. , Land W. , Schildberg F.W.
Published: April 2003

Background: In the present study, a technique for computer-assisted, normothermic, oxygenated, ex vivo, recirculating small bowel perfusion was established as a tool to investigate organ pretreatment protocols and ischemia/reperfusion phenomena. A prerequisite for the desired setup was an organ chamber for ex vivo perfusion and the use of syngeneic whole blood as perfusate. Methods: The entire small bowel was harvested from Lewis rats and perfused in an organ chamber ex vivo for at least 2 h. The temperature was kept at 37°C in a water bath. Three experimental groups were explored, characterized by different perfusion solutions. The basic perfusate consisted of syngeneic whole blood diluted with either NaCl, Krebs’ solution or Krebs’ solution and norepinephrine to a hematocrit of 30%. In addition, in each group l-glutamine was administered intraluminally. The desired perfusion pressure was 100 mm Hg which was kept constant with a computer-assisted data acquisition software, which measured on-line pressure, oxygenation, flow, temperature and pH and adjusted the pressure by changing the flow via a peristaltic pump. The viability of the preparation was tested by measuring oxygen consumption and maltose absorption, which requires intact enzymes of the mucosal brush border to break down maltose into glucose. Results: Organ perfusion in group 1 (dilution with NaCl) revealed problems such as hypersecretion into the bowel lumen, low vascular resistance and no maltose uptake. In contrast a viable organ could be demonstrated using Krebs’ solution as dilution solution. The addition of norepinephrine led to an improved perfusion over the entire perfusion period. Maltose absorption was comparable to tests conducted with native small bowel. Oxygen consumption was stable during the 2-hour perfusion period. Conclusions: The ex vivo perfusion system established enables small bowel perfusion for at least 2 h. The viability of the graft could be demonstrated. The perfusion time achieved is sufficient to study leukocyte/lymphocyte interaction with the endothelium of the graft vessels. In addition, a viable small bowel, after 2 h of ex vivo perfusion, facilitates testing of pretreatment protocols for the reduction of the immunogenicity of small bowel allografts.
Preparation of a Skeletal Muscle Ventricle in Sheep: Severe Damage to the Latissimus dorsi Muscle due to Mobilization before Preconditioning
Authors: Lanmüller H. , Girsch W. , Rab M. , Sauermann S. , Kamolz L.-P. , Seitelberger R. , Wolner E.
Published: April 2003

As part of a study examining the use of a skeletal muscle ventricle for cardiac assistance in sheep, a new concept of muscle preconditioning was put into practice. We aimed to produce a latissimus dorsi muscle (LDM) capable of performing chronic work immediately after the construction of a skeletal muscle ventricle. The left LDM was detached from the thoracic wall, divided longitudinally and reattached in situ to achieve vascular delay. The right LDM was left unaffected. Thereafter, preconditioning of both LDM was started according to the clinically approved stimulation protocol for cardiomyoplasty. Preconditioning of the unaffected right LDM in situ resulted in a complete muscle fiber transformation with no signs of degeneration or necrosis. Mobilization of the left LDM before preconditioning led to a distinct damage of the muscle. During conditioning, the increase in burst duration from 2 to 3 impulses in sheep A and from 3 to 5 impulses in sheep B resulted in a homogenous degeneration of the muscle fibers of the left LDM. Histomorphological analysis showed a dramatic increase in the percent perimysial and endomysial connective tissue. The applied concept of muscle prefabrication proved to be a failure. Muscle splitting and mobilization followed by vascular delay and in situ conditioning as a concept of muscle prefabrication should be strictly avoided.
Beneficial Effects of Prostaglandin E1 Incorporated in Lipid Microspheres on Liver Injury and Regeneration after 90% Partial Hepatectomy in Rats
Authors: Ando K. , Miyazaki M. , Shimizu H. , Okuno A. , Nakajima N.
Published: April 2003

The aim of this study was to assess how the administration of prostaglandin E1 incorporated in lipid microspheres (Lipo PGE1) affects liver injury and regeneration after massive hepatectomy in rats. Two hundred and eight male Wistar rats underwent 90% partial hepatectomy. Lipo PGE1 of 1, 10 or 30 μg/kg were administered intraperitoneally at 6 h prior to and 0 and 6 h after hepatectomy. Postoperative increases in serum GOT, total bilirubin, IL-6 and plasma endotoxin levels were significantly suppressed by Lipo PGE1. The depressed phagocytic index and arterial ketone body ratio and hepatic DNA synthesis after 90% partial hepatectomy were significantly enhanced by Lipo PGE1, which resulted in the improvement of survival. Lipo PGE1 might bring about a protective effect on liver injury and an enhancement of liver regeneration after massive hepatectomy.
A Novel Auxiliary Partial Orthotopic Liver Transplantation Model in Rats
Authors: Ikegami T. , Nishizaki T. , Yanaga K. , Ohta R. , Hiroshige S. , Sugimachi K.
Published: April 2003

Background: Although auxiliary partial orthotopic liver transplantation (APOLT) has become a well-accepted procedure recently, a practical experiment model in APOLT using small animals has yet to be developed. Methods: Male Lewis rats were used for both donors and recipients. An auxiliary partial graft was obtained by ex vivo resection of the donor right and caudate lobes, and was transplanted orthotopically into the recipient after resection of the recipient medial and left hepatic lobes. Portal vein and hepatic duct reconstructions were by the cuff technique, and supra- and intrahepatic vena cava were sutured continuously. Operative outcomes, serum chemistry, liver tissue blood flow, angiographic and histopathological findings were then examined. Conventional orthotopic liver transplantation (OLT) procedures were also undertaken as a control. Results: One-day, 1-week and 1-month survival rate of APOLT group was 100, 85 and 85%, respectively. AST in the APOLT group on the 1st postoperative day was significantly higher than in the OLT group. No significant differences were recognized in serum albumin and total bilirubin levels between the two groups. Although the portogram of an APOLT rat showed slight narrowing at the cuff anastomosis site, both the graft and the native liver were opacified similarly. The liver tissue blood flow on the 5th postoperative day in the native liver and the graft returned to as high as 95 and 74% of the values on laparotomy, respectively. Histological examinations of the auxiliary graft 1 month after transplantation showed mild ductular proliferation and mononuclear cell infiltration around the portal triads. Conclusion: This novel APOLT model in rats allows practical and reproducible results, and may be of value in the basic study of APOLT procedures.
Amniotic Membrane as an in vitro Model for Endometrium- Extracellular Matrix Interactions
Authors: van der Linden Paul J.Q. , de Goeij Anton F.P.M. , Dunselman Gerard A.J. , Erkens Heleen W.H. , Evers Johannes L.H.
Published: April 2003

The aim of the study was to develop an in vitro model to study the interaction between endometrial cells and extracellular matrix (ECM) and to evaluate the expression of cell adhesion molecules in endometrial cells and tissue fragments under in vitro conditions. Endometrial biopsies were collected from 32 patients. Samples were either digested using collagenase type I, or dissected mechanically. Adhesion of isolated cells and tissue fragments to stripped amniotic membranes and to coverslips coated with ECM components was studied. The expression of β1 integrins and cadherins was assessed using immunohistochemistry. Collagenase digestion of endometrial biopsies yielded viable single cells. These cells did not adhere to either side of stripped amniotic membranes, and did not show expression of the cell adhesion molecules. In contrast, mechanically fragmented endometrium samples adhered to both sides of stripped amniotic membranes and showed immunohistochemical expression of E- and P-cadherin and integrin subunits α2, α3, α4, α5 and α6. Amniotic membranes, after stripping of epithelial lining, are suitable to study interactions between endometrial tissue and ECM in functional and structural studies. Endometrial cells after collagenase type I digestion do not adhere to stripped amniotic membrane and have lost expression of β1 integrins and E- and P-cadherin.
Chromosomal Mosaicisms during Prenatal Diagnosis
Authors: Verma Ram S. , Kleyman Svetlana M. , Conte Robert A.
Published: April 2003

Chromosomal mosaicism during prenatal diagnosis has been a major concern. Nondisjunctional events can lead to mosaicism in a number of ways, including failure of chromosomal pairing, failure to separate, anaphase lag and abnormal segregation. We provide a concise review on various types of mosaicism with their clinical significance.
Evaluation of a New Portable System for Cord Lactate Determination
Authors: Yam J. , Chua S. , Razvi K. , Arulkumaran S.
Published: April 2003

To evaluate a new reflectance photometer (Accusport®) for blood lactate determination, a prospective non-interventional study was performed on blood obtained from the umbilical cord artery immediately after delivery of the baby in 109 consecutive women. For each sample, the results of cord arterial blood lactate values measured with the reflectance photometer were compared with those obtained using a reference method in the laboratory. The values obtained using Accusport were comparable in accuracy with those obtained using a laboratory reference method (Ektachem 9501RC). The instrument provides a simple and reliable method for determining cord arterial blood lactate levels in a small blood sample.
Stimulated Polymorphonuclear Leukocytes in Vaginal Secretions from Patients with Preterm Labor
Authors: Matsubara Shigeki , Yamada Tetsuo , Minakami Hisanori , Sato Ikuo
Published: April 2003

The purpose of this study was to examine evidence for the presence of activated vaginal leukocytes in women with preterm labor. Vaginal polymorphonuclear leukocytes from 7 patients in preterm labor (24–32 weeks of gestation) as well as from 7 control women with uncomplicated pregnancy were analyzed morphologically using transmission electron microscopy. Peroxidase and NADPH oxidase cytochemistry was also performed. Viable leukocytes were abundant in patients in preterm labor. Phagosomes, phagocytosis of bacteria, attachment of primary granules to the phagosomal membrane, and cell surface projections were observed in the vaginal leukocytes but not in the peripheral blood leukocytes. Peroxidase activity was visible on the cell surface, the phagosomal membrane, and the primary granules. NADPH oxidase activity was demonstrated on the cell surface of leukocytes. Morphological and cytochemical features indicated that vaginal polymorphonuclear leukocytes were stimulated in situ. Such stimulated leukocytes may play a role in the pathogenesis or pathophysiology of preterm labor.
Postpartum Uterine-Artery Velocity Waveforms in Women with Sickle Cell Disease
Authors: Anyaegbunam A. , Garcia J. , Mikhail M.S.
Published: April 2003

Objective: To investigate the changes in uterine Doppler velocimetry during the postpartum period in women with homozygous sickle cell (SS) disease and to correlate these findings with values in the third trimester and with neonatal outcomes. Methods: We studied the postpartum changes in uterine Doppler velocimetry in 16 women with SS disease in relation to third-trimester systolic/diastolic (S/D) ratios and neonatal outcome. All patients had repeated measures of uterine S/D ratios biweekly in the third trimester from 28 weeks of pregnancy until delivery, and at 24 h, and 3 and 6 weeks postpartum. Results: Overall the mean S/D ratio in the first 24 h for these 16 women was 2.72 ± 0.72 and increased progressively to a mean S/D ratio of 6.88 ± 0.96 at 6 weeks postpartum, with the reappearance of a diastolic notch by the 3rd postpartum week. Twelve women who had normal (≤2.6) uterine S/D ratios during pregnancy delivered appropriate-for-gestational-age (AGA) infants. The remaining 4 women had abnormal uterine S/D ratios, and in 3 of these pregnancies, small-for-gestational-age (SGA) infants were delivered. The mean S/D ratios for the subgroups with abnormal value at each of the three postpartum periods were significantly higher than for the 12 SS patients with normal third-trimester values. Postpartum S/D ratios for the 3 women with SGA births were also significantly higher at 24 h and 6 weeks postpartum when compared to SS patients with AGA infants. Conclusion: We concluded that postpartum S/D ratios are higher in women with SS disease that have abnormal values in the third trimester and that they are associated with SGA births. In SS patients the nonpregnant pattern of uterine artery velocity waveforms which reappears postpartum may reflect an increase in the uteroplacental circulatory impedence due to reversal of the alterations in the spiral arteries induced by trophoblastic invasion during pregnancy or subinvolution of the placental bed. Additional studies are needed to further elucidate these important hemodynamic changes in women with hemoglobinopathies and to identify patterns predictive of neonatal outcomes in these high-risk patients.
Elevation in Plasma Alkaline Phosphatase Level during rhG-CSF Administration
Authors: Fukumasu Hiroshi , Fukumasu Yasuko , Ogita Sachio
Published: April 2003

Neutropenic patients suffering from gynecologic cancers treated with cancer chemotherapy were evaluated to investigate changes in levels of plasma alkaline phosphatase (ALP) during recombinant human granulocyte colony stimulating factor (rhG-CSF) administration, and to discern its causes. Plasma ALP, ALP isozymes, neutrophil alkaline phosphatase (NAP) activity, and morphological maturation of neutrophils were measured prior to, during, and after rhG-CSF administration. Plasma ALP values were significantly elevated (p < 0.05) during administration of rhG-CSF. ALP-3, the dominant alkaline phosphatase fraction of NAP, was the dominant isozyme that showed an increase in the plasma. Moreover, the elevation of plasma ALP-3 significantly correlated with the elevation of NAP activity (r = 0.939, p < 0.0001), and neutrophils in which NAP activity was induced were not limited to morphologically mature neutrophils. These results showed that rhG-CSF acts to stimulate neutrophils at all stages of maturation and causes an elevation of plasma ALP(ALP-3) concentrations in plasma.
Endometrium-to-Myometrium Relative Echogenicity Coefficient
Authors: Leibovitz Zvi , Degani Shimon , Rabia Ron , Tal Joseph , Eibchitz Izu , Shapiro Israel , Paltieli Yoav , Aharoni Ariel , Steinkuler Meir , Ohel Gonen
Published: April 2003

A computer program was developed to assess the endometrial echogenicity relative to the myometrial one, based on the gray-level processing of the midsagittal uterine image. The endometrial region of interest was specified within the upper part of the uterine cavity. The adjacent area of the myometrium was used to determine the reference brightness. The endometrial region of interest was analyzed along the anteroposterior uterine axis, as a set of thin strips directed parallelly to the midcavitary line. The endometrial/myometrial relative echogenicity coefficient (E/M REC) was computed for each strip and displayed graphically as a function of the distance from the midcavitary line. The area under the E/M REC curve within the limits of the total endometrial width was defined as total area (TA) and was used as a measure of the endometrial echogenicity. This parameter was assessed in 9 patients during their normal ovulatory cycles and in 29 IVF-treated patients with mechanical infertility. TA has a significant linear increase during the days of the ovulatory cycles. TA was found in high correlation with log(estradiol). TA can be used reliably for sonographic endometrial dating in ovulatory cycles.
Paraneoplastic Cerebellar Degeneration with Anti-Purkinje Cell Antibody Associated with Primary Tubal Cancer
Authors: Matsushita Hiroshi , Kodama Shoji , Aoki Yoichi , Tanaka Kenichi , Tanaka Kunio , Saito Noriyasu
Published: April 2003

In patients with paraneoplastic cerebellar degeneration (PCD) due to gynecologic malignancies, a high titer of anti-Purkinje cell antibody (anti-Yo) has been found. Most patients, however, have limited oncologic disease at the time of onset of neurologic symptoms. We describe 2 cases of PCD due to tubal cancer with anti-Yo antibody. The onset of PCD occurred 4 and 14 months before the detection of cancer, respectively, and the presence of anti-Yo antibody facilitated early laparotomy in both cases. These patients, whose neurologic symptoms have not progressed, have survived without evidence of disease for 81 and 30 months since surgery, respectively. The presence of the anti-Yo antibody in patients with PCD warrants an aggressive approach to diagnosis and treatment of the underlying gynecologic cancer.
Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium
Authors: Adolfsson Per I. , Dahle Lars Olav , Berg Göran , Svensson Samuel P.S.
Published: April 2003

The aim of the present investigation was to determine which subtypes of the α2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 ± 0.6 nM and Bmax of 95 ± 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (α2A-subptype), chlorpromazine (α2B-subtype) and prazosin (α2B-α2C-subtype), suggested that the α2A- and α2B-subtypes are being co-expressed. In order to examine if also the α2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α2A- and α2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α2C-subtype also is being expressed. The expression of α2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.In conclusion, our results suggest that all three subtypes of α2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α2-expression is dominated by the α2A-subtype.
Evaluation of Glucose Intolerance in Pregnancy Using Biochemical Markers of Fetal Hyperinsulinemia
Authors: Roach Vijay J. , Fung Hedy , Cockram Clive S. , Lau T.K. , Rogers Michael S.
Published: April 2003

We aimed to evaluate gestational impaired glucose tolerance (GIGT) in untreated patients using umbilical cord blood insulin and connecting peptide (C-peptide) concentrations to indicate fetal hyperinsulinemia. A 75 g, 2-hour oral glucose tolerance test, evaluated using WHO criteria, was performed in 722 antenatal patients. Cord C-peptide (p = 0.001) and insulin (p = 0.008) concentrations were significantly higher in patients with GIGT in comparison to those with normal glucose tolerance. The WHO test failed to identify abnormal C-peptide concentrations (p = 0.057), but did identify abnormal insulin concentrations (p = 0.006) and cases where either or both were raised (p = 0.002), with a low Youden’s index (range 8.1–11.3) in all 3 cases. A significant biochemical difference exists in patients with GIGT. The WHO criteria for GIGT predict abnormal biochemical outcomes, but they do so poorly.