Functional deficits and morphological changes in the neurogenic bladder match the severity of spinal cord compression.

UNLABELLED: Following spinal cord injury (SCI), loss of spinal and supraspinal control results in desynchronisation of detrusor vesicae (parasympathicus) and external urethral sphincter (sympathicus) activity. Despite recovery of lower urinary tract function being a high priority in patients with SCI, effective treatment options are unavailable largely because mechanisms are poorly understood. PURPOSE AND METHODS: We used a clinically relevant model of thoracic SCI compression injury in adult female Wistar rats and confirmed that lesion volumes following severe injuries were significantly greater compared to moderate injuries (p < 0.05). Between 1-9 weeks, we assessed recovery of bladder function as well as return of locomotor function using the Basso, Beattie and Bresnahan (BBB) score. Bladder morphometrics and overall intramural innervation patterns, as assessed with ß-III tubulin immunohistochemistry, were also examined. RESULTS: Despite variability, bladder function was significantly worse following severe compared to moderate compression injury (p < 0.05); furthermore, the degree of bladder and locomotor dysfunction were significantly correlated (r = 0.59; p < 0.05). In addition, at 9 weeks after SCI we saw significantly greater increases in bladder dry weight (p < 0.05) and wall thickness following severe compared to moderate injury as well as increases in intramural axon density (moderate: 3× normal values; severe 5×; both p < 0.05) that also correlated with injury severity (r = 0.89). CONCLUSION: The moderate and severe compression models show consistent and correlated deficits in bladder and locomotor function, as well as in gross anatomical and histopathological changes. Increased intramural innervation may contribute to neurogenic detrusor overactivity and suggests the use of therapeutic agents which block visceromotoric efferents.

Effect of gossypol on blood serum parameters and small intestinal morphology of male broilers.

Summary In the present study, the effect of varied gossypol (GOSS) amounts was investigated on blood parameters, the digesta pH, villus height, villus width, and crypta depth, width of duodenum, jejunum and ileum. A total of one hundred eight Ross 308 male broilers were fed with four diet groups as follows: no gossypol (control), gossypol rate 62 mg/kg (GOSS 62), gossypol rate 124 mg/kg (GOSS 124) and gossypol rate 186 mg/kg (GOSS 186). The effect of used gossypol amounts on blood parameters was not found to be statistically significant. Increases in digesta pH values of jejunum and ileum with GOSS 186 diet group were found to be statistically significant. The results also indicated that, except duodenum villus height, there was no statistical difference effect of GOSS on epithelial cell thickness, villus height, villus width, crypta depth and crypta width of the duodenum, jejunum and ileum. There have been no clearly negative effects of higher gossypol amounts up to 186 mg/kg diets on these parameters.

Behavioral deficits and cellular damage following developmental ethanol exposure in rats are attenuated by CP-101,606, an NMDAR antagonist with unique NR2B specificity.

NMDAR-mediated excitotoxicity has been implicated in some of the impairments following fetal ethanol exposure. Previous studies suggest that both neuronal cell death and some of the behavioral deficits can be reduced by NMDAR antagonism during withdrawal, including antagonism of a subpopulation of receptors containing NR2B subunits. To further investigate NR2B involvement, we selected a compound, CP-101,606 (CP) which binds selectively to NR2B/2B stoichiometries, for both in vitro and in vivo analyses. For the in vitro study, hippocampal explants were exposed to ethanol for 10 days and then 24 h following removal of ethanol, cellular damage was quantified via propidium iodide fluorescence. In vitro ethanol withdrawal-associated neurotoxicity was prevented by CP (10 and 25 nM). In vivo ethanol exposure was administered on PNDs 1-7 with CP administered 21 h following cessation. Activity (PNDs 20-21), motor skills (PNDs 31-33), and maze navigation (PNDs 43-44) were all susceptible to ethanol insult; treatment with CP (15 mg/kg) rescued these deficits. Our findings show that CP-101,606, a drug that blocks the NR2B/2B receptor, can reduce some of the damaging effects of "3rd trimester" alcohol exposure in our rodent model. Further work is clearly warranted on the neuroprotective potential of this drug in the developing brain.

Lobeline attenuates neonatal ethanol-mediated changes in hyperactivity and dopamine transporter function in the prefrontal cortex in rats.

Current therapies for attention deficit hyperactivity disorder (ADHD) have varying efficacy in individuals with fetal alcohol spectrum disorders (FASD), suggesting that alternative therapeutics are needed. Developmental exposure to ethanol produces changes in dopamine (DA) systems, and DA has also been implicated in ADHD pathology. In the current study, lobeline, which interacts with proteins in dopaminergic presynaptic terminals, was evaluated for its ability to attenuate neonatal ethanol-induced locomotor hyperactivity and alterations in dopamine transporter (DAT) function in striatum and prefrontal cortex (PFC). From postnatal days (PND) 1-7, male and female rat pups were intubated twice daily with either 3 g/kg ethanol or milk, or were not intubated (non-intubated control) as a model for "third trimester" ethanol exposure. On PND 21 and 22, pups received acute lobeline (0, 0.3, 1, or 3 mg/kg), and locomotor activity was assessed. On PND 23-25, pups again received an acute injection of lobeline (1 or 3 mg/kg), and DAT kinetic parameters (Km and V(max)) were determined. Results demonstrated that neonatal ethanol produced locomotor hyperactivity on PND 21 that was reversed by lobeline (1 and 3 mg/kg). Although striatal DAT function was not altered by neonatal ethanol or acute lobeline, neonatal ethanol exposure increased the V(max) for DAT in the PFC, suggesting an increase in DAT function in PFC. Lobeline ameliorated this effect on PFC V(max) at the same doses that decreased hyperactivity. Methylphenidate, the gold standard therapeutic for ADHD, was also evaluated for comparison with lobeline. Methylphenidate decreased DAT V(max) and Km in PFC from ethanol-treated pups. Thus, lobeline and methylphenidate differentially altered DAT function following neonatal ethanol exposure. Collectively, these findings provide support that lobeline may be a useful pharmacotherapy for some of the deficits associated with neonatal ethanol exposure.

Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure.

This study examined the effects of binge-like ethanol (ETOH) exposure in neonatal rats on a cerebellar-mediated balance task, and the ability of agmatine, an n-methyl-d-aspartate receptor (NMDAR) modulator, to reverse such effects. Five neonatal treatments groups were used, including ETOH (6.0 g/kg/day), AG (20 mg/kg), ETOH plus AG (6.0 g/kg/day and 20 mg/kg), a maltose control, and a non-treated control. Ethanol was administered via oral intubation twice daily for eight days, (AG was administered with the last ETOH intubation only). Two exposure periods were used; PND 1-8 or PND 8-15. On PND 31-33, balance performance on a single dowel was tested. Treatment with AG during withdrawal in ETOH exposed animals improved performance relative to ETOH alone among the PND 1-8 exposure period. ETOH exposure during the 2nd postnatal week did not impair balance. These findings provide further support that exposure to ETOH during critical developmental periods can impair performance on a cerebellar-dependent balance task. Of perhaps greater significance, co-administration of agmatine reduced these deficits suggesting that NMDA modulation via polyamine blockade may provide a novel approach to attenuating damage associated with binge-like ETOH consumption.

[Malignant gastrointestinal stromal tumor (GIST) of the papilla vateri. A rare tumor entity]. / Maligner gastrointestinaler Stromatumor (GIST) der Papilla vateri. Eine seltene Tumorentität.

We present the case report of a 68-year-old female patient who had a malignant gastrointestinal stromal tumor of the papilla of Vater. The abdominal CT showed a coin-shaped lesion in the liver (segment VIII). Intraoperative rapid histological examination detected an old parasitic hepatic cyst. To exclude metastasis, we performed duodenopancreatectomy with curative intention. The postoperative course was without complications and neither chemotherapy nor other adjunct treatment was necessary. Because of heterogeneity, the different localization, and in this case the rare localization, surgery of gastrointestinal stromal tumors is difficult. However, we adhered to oncological and therapeutic standards of surgery for papillary carcinoma. This case is discussed based on a review of the literature. However, until now there has been no case report of gastrointestinal stromal tumor of the papilla of Vater in the literature.

[Dependence of surgical trauma in aortic interventions on the approach chosen. A prospective study]. / Die Abhängigkeit des Operationstraumas bei Aorteneingriffen von dem gewählten Zugang. Eine prospektive Studie.

Transabdominal aortic replacement is the most widely accepted approach for aortic surgery. Several controlled studies report a more favorable outcome after an extraperitoneal incision, yet there are an equal number of papers with contradictory results. The aim of our study was to assess operative trauma after aortic surgery, depending on whether transperitoneal or extraperitoneal access was used. As a parameter for the extent of the surgical trauma the concentration of Interleukin 6 and acute phase proteins (CRP) was measured pre-, 6 h and 24 h after aortic surgery. One group consisted of 34 patients scheduled for aortic surgery for exclusion of an abdominal aortic aneurysm. The second group consisted of 26 patients who were operated on for aorto-iliac occlusive disease. Each group was subdivided into an equal group of patients operated on either extra- or transperitoneally. In the retroperitoneal aneurysm patients, a posterolateral access was favored, and in patients with occlusive disease an extraperitoneal anterolateral approach was chosen. As a result patients with an extraperitoneal incision and aorto-iliac occlusive disease required less postoperative respiratory support than those operated on transperitoneally. In this subgroup of patients there was a significantly reduced synthesis of Interleukin 6 and CRP. When a retroperitoneal posterolateral approach was required in aneurysm patients, there was no difference between groups. We conclude from our data that only patients with limited infrarenal aortic access can benefit, from the retroperitoneal incision in terms of a reduced immunological reaction.

[Laparoscopy-assisted aortoiliac reconstructions]. / Laparoskopisch assistierte aortoiliakale Rekonstruktionen.

Five patients underwent an aortobifemoral bypass using a laparoscope-assisted procedure. With the help of a wall-lifting device, balloon dissection of the retroperitoneum was performed. A total number of five ports were inserted and the aorta was dissected out from the bifurcation to the renal arteries under the guidance of a laparoscopic video camera. A 5-cm incision was required for suturing the proximal anastomosis of the bifurcated graft. Tunneling from the groin to the aorta was performed either video-assisted or with the help of the balloon dissector with a camera inside. All patients could be fully mobilized on the first postoperative day and were discharged after a mean hospital stay of 7.6 days. Mean length of the operation was 250 min. Originally, seven patients were scheduled for the video-assisted procedure. In two cases, we had to change to a conventional technique: in one case because we could not achieve adequate exposure of the aorta in an obese patient using a transperitoneal access, and in the second case owing to extensive adhesions after a bowel resection. Both patients had a regular, uneventful postoperative course. Gasless laparoscopy allowed us to use standard surgical instruments and most importantly a regular aortic clamp, which proved to be beneficial in a heavily calcified aorta. In conclusion, retroperitoneal gasless laparoscopic procedures can be safely performed in infrarenal aortoiliac reconstructions. Further clinical studies are required to prove the usefulness of this new technique.

North American Indian rock art and hallucinogenic drugs.

It is proposed that the aboriginal rock paintings in two areas of North America may have been produced by shamans while they were under the influence of hallucinogenic agents derived from plants. The first of these areas is the Chumash and Yokuts Indian region of California, where polychrome paintings show designs similar to those visualized during the trance induced by decoctions of jimsonweed (Datura species). The second area is the lower Pecos River region of Texas, where shamanistic figures display traits considered to be conceptual analogues of the mescal bean (Sophora secundiflora) cult as practiced during historic times by Great Plains Indians. Although the evidence is only circumstantial, the proposed connections between these rock drawings and mind-expanding pharmacologic compounds fit well into the documented relationship that encompasses hallucinogenic drugs and certain movable objects of pre-Columbian American art.

Modification of streptozotocin-induced diabetes in rats by pretreatment with cortisone.

Cortisone pretreatment considerably enhances the mortality of young, male, streptozotocin-injected Holtzman rats. In those that survive, cortisone pretreatment decreases the ensuing hyperglycaemia, extends the period during which streptozotocin-induced B cell damage can be observed from less than two to as much as four to seven days and permits the persistence of poorly granulated B cells in such animals. These effects are at least partially attributable to a cortisone-induced augmentation of the total B cell mass. Compared with the high degree of protection against alloxan-induced damage afforded the pancreatic B cells of cortisone-pretreated rabbits, the protective effect of cortisone against B cell destruction in streptozotocin-injected rats is thus much more limited in scope. Species differences as well as differing pathogenetic mechanisms may account for these results.

Nodular intercapillary glomeruloscerosis in diabetes secondary to chronic calcific pancreatitis.

Nodular (specific) intercapillary glomerulosclerosis (Kimmelstiel-Wilson) was found at autopsy in a 47-year-old man who had been diabetic for 20 years. The family history for this disease had been negative. Both the clinical course and the autopsy findings strongly suggest that this patient's diabetes was secondary to chronic fibrocalcific pancreatitis. This is only the fourth recorded case of histologically documented nodular glomerulosclerosis occurring in a patient with pancreatogenic diabetes.

Fine structure of pancreas in cortisone-treated guinea pigs and rabbits.

Twenty-eight male rabbits and 28 male guinea pigs received daily intramuscular injections of cortisone acetate for four to 31 days (rabbits, 5 mg/kg; guinea pigs, 10 mg/animal). Moderate hyperglycemia ensued. Insulin concentrations of the pancreatic tissue varied but were higher in cortisone-treated animals than in untreated controls. In rabbits, degranulation of beta cells, hyperplasia of islets, and proliferation of ductular structures were the major light microscopic findings. Ultrastructural studies suggested that beta cell neogenesis took place mainly within pre-existing islets but probably also within ductular structures. Mixed (acinar-islet) cells were not identified. In guinea pigs, ductular proliferation was not noted, and beta cell neogenesis appeared to take place exclusively within preexisting islets and islet cell nests. In both species, cells of several types contained glycogen deposits.

[Pathology in the U.S.A. A glut of pathologists, the role of the autopsy and the future of the "clinical pathology"]. / Zur Situation der Pathologie in den U.S.A. Pathologenschwemme, die Rolle der Autopsie und die Zukunft der "klinischen Pathologie"

This analysis deals with selected questions regarding the status of pathology in the United States. For a long time, the number of pathologists, both in practice and in training, had been deemed inadequate, but present trends indicate the existence of a considerable surplus of specialists in this discipline. The autopsy is still an important field of endeavor for the American pathologist even tbhough autopsy rates have drastically declined everywhere and the exact role of this procedure is being reevaluated. The concept of "clinical pathology" which seeks to encompass a whole conglomerate of heterogeneous disciplines and still dominates the practice of pathology in North America has come under attack; some observers plead for the total separation of laboratory medicine from pathology as well as for the systematic and intensive development of subspecialties within the field of pathology.