Neurohumoral control of gallbladder motility in healthy subjects and diabetic patients with or without autonomic neuropathy

Patients affected by diabetes mellitus are reported to have an increased incidence of gallbladder abnormalities. The pathophysiologic mechanisms for this phenomenon are unclear. In the present study ultrasonography was used to determine gallbladder emptying in response to a meal or separate cephalic or hormonal stimulation in 21 diabetic patients and 10 healthy subjects. Gallbladder emptying and refilling after a meal were similar in diabetic patients and healthy subjects. When diabetics were divided according to the presence or absence of cardiac autonomic neuropathy (AN), a significant reduction of gallbladder emptying in response to cephalic stimulation was found in diabetics with AN (P<0.01 in comparison with diabetics without AN or healthy subjects). A dose-response curve of gallbladder emptying in response cerulein, a cholecystokinin analog, at concentrations of 0.25, 1, and 4 g/kg/min was evaluated. No differences of gallbladder emptying were found in the three groups of subjects, indicating that gallbladder sensitivity to hormonal stimulation is not changed in diabetic patients with or without AN. Diabetic patients with AN have a significant reduction of gastric acid output and pancreatic polypeptide (PP) secretion in response to cephalic stimulation (P<0.05 in comparison with diabetic patients without AN or healthy subjects). Cerulein-induced PP secretion was similar in all three groups of subjects (P>0.05). This study indicates that in diabetic patients with AN, gallbladder emptying as well as gastric acid and PP secretions induced by neural stimulation are markedly reduced in comparison to diabetics without AN.     

Serotonergic inhibition of the mossy fibre—granule cell glutamate transmission in rat cerebellar slices

Summary The glutamatergic mossy fibre granule cell pathway has been investigated in rat cerebellar slices. Exposure to 35 mM KCI, a concentration of K⁺ known to elicit Ca²⁺-dependent releases of excitatory amino acids from cerebellar slices, raised cGMP levels. The cGMP response was decreased in a concentration-dependent manner by D-(–)-2-amino-5-phosphonopentanoic acid (D-AP5) and by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) indicating the involvement of ionotropic glutamate receptors of both the N-methyl-D-aspartate (NMDA) and the non-NMDA type. The K⁺-evoked production of cGMP was potently inhibited (EC₅₀ = 1.21 nM) by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a selective 5-HT₂ receptor agonist. The effect of DOI (0.01 M) was antagonized by 0.03 M of the 5-HT₂ receptor antagonists ketanserin and methiothepin. At concentrations higher than 0.1 M, both antagonists increased on their own the cGMP response elicited by high-K⁺. This effect was insensitive to tetrodotoxin.It had been previously shown that rat mossy fibre endings release glutamate upon depolarization and that such release can be inhibited by activation of 5-HT₂ receptors sited on the mossy fibre endings. Altogether the available data suggest the following conclusions: (a) the glutamate/aspartate endogenously released in cerebellar slices during K⁺ depolarization increase cGMP synthesis through the activation of both NMDA and non-NMDA receptors; (b) a portion of the cGMP response can be prevented by 5-HT₂ receptor activation and may reflect the activity of the mossy fibre-granule cell pathway. Thus serotonin is likely to exert a potent inhibitory control of the excitatory mossy fibre input to the cerebellum by acting at receptors of the 5-HT₂ type. Correspondence to M. Raiteri at the above address     

Strain-dependent effects of post-training GABA receptor agonists and antagonists on memory storage in mice

Post-training administration of the GABA-A and GABA-B receptor agonists muscimol and baclofen dose-dependently impaired retention of an inhibitory avoidance response in C57 mice, while improving memory consolidation in the DBA strain. By contrast, picrotoxin (blocker of GABA-activated ionophores), bicuculline (GABA-A antagonist) and CGP 35348 (GABA-B antagonist) dose-dependently improved retention in C57 mice and impaired it in DBA mice. These effects cannot be ascribed to non-specific actions of the drugs on retention performance, as the latencies during the retention test of those mice that had not received footshock during the training were not lengthened by the post-training drug administration. The effects on retention performance induced by GABA agonists and antagonists are probably due to an effect on memory consolidation, since they are observed when the drugs are given at short, but not at long, intervals after training. These results are discussed in terms of possible interaction of GABA systems with endogenous opioid and dopamine systems, whose activation has been shown to produce strain-dependent effects on memory processes. The possible utilization of these results for a genetic behavioral approach with recombinant inbred (RI) mice is also considered.     

Coloanal anastomosis after resection of low rectal cancer in the elderly

Twenty-two patients had coloanal anastomoses performed after resection of low rectal tumors (16 adenocarcinomas and 6 large degenerated villous adenomas). The patients had an average age of 72 years (range: 62–85). A hand-sewn anastomosis was performed between a J-shaped colonic reservoir and the anal sphincter, except in 3 patients who underwent a straight end-to-end coloanal suture without pouch. A defunctionalized stoma was made in 18 cases. Mortality within 30 days of operation was 9%. Specific complications occurred in 2 patients (9%). Mean follow-up in this series was 20.2±11.7 months (± standard deviation). Fifteen patients were alive and free of disease up to 54 months after surgery. One patient was found to have local recurrence at 19 months. The actuarial 3-year survival rate was 73% in the whole group (operative mortality included). Functional results were good in 16 of 19 patients, with an average 1.8–2.9 stools/24 hours and the continence rate was good. Three patients had complications requiring a permanent colostomy. From these preliminary results, coloanal anastomosis appears to be satisfying in regard to oncologic results and affords good anal function, even in the elderly patient (over 62 years of age).

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Resumen Veintidos pacientes fueron sometidos a anastomosis después de la resecciôn de tumores rectales bajos (16 adenocarcinomas y 6 grandes adenomas vellosos con degeneración carcinomatosa), con edad promedio de 72 años (rango: 62–85). Se practicó anastomosis manual entre un reservorio colónico construído en forma de J y el esfínter anal, excepto en 3 pacientes sometidos a sutura colo-anal términoterminal sin construcción de bolsa. Se practicó un estoma de funcionante en 18 casos. La mortalidad en los primeros 30 días después de la operación fue 9%. Se presentaron complicaciones específicas en 2 pacientes (9%). El seguimiento promedio en la serie fue de 20.2±11.7 meses (± de). Quince pacientes se encuentran vivos y libres de enfermedad hasta por 54 meses. Un paciente demostró recurrencia local a los 19 meses. La tasa actuarial de sobrevida a 3 anos es de 73% para el grupo total (incluyendo la mortalidad operatoria). Los resultados funcionales fueron buenos en 16 de 19 pacientes, con un promedio de 1.8 a 2.9 deposiciones/24 horas y buena continencia. Tres pacientes presentaron complicaciones que requirieron colostomía permanente. Según estos resultados preliminares, la anastomosis colo-anal aparece como un procedimiento satisfactorio en relación con los resultados oncológicos y provee buena función anal aun en el paciente anciano (mayor de 62 años).

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Résumé Vingt-deux patients ont eu une anastomose coloanale après résection d'une tumeur rectale basse (16 adénocarcinomes et 6 tumeurs villeuses larges dégénérées). L'âge moyen des patients était de 72 ans (extrêmes 62 et 85 ans). Dix-neuf patients ont eu une anastomose manuelle entre un réservoir colique en J et le canal anal, alors que 3 ont eu une anastomose manuelle termino-terminale coloanale sans réservoir. Une colostomie de décharge a été ajoutée dans 18 cas. La mortalité des 30 premiers jours postopératoires a été de 9%. Deux patients (9%) ont eu des complications spécifiques. La survie moyenne a été de 20.2±11.7 mois (± ET). A 54 mois, 15 patients sont en vie et sans maladie. Une récidive locale a été décelée chez un patient à 19 mois. La survie actuarielle à 3 ans est de 73% pour l'ensemble des patients (mortalité opératoire incluse). Les résultats fonctionnels étaient bons chez 16 des 19 patients. Ces patients avaient en moyenne 1.8 à 2.9 selles par 24 heures et la continence était bonne. Trois patients avaient des complications nécessitant une colostomie permanente. D'après ces premiers résultats, il semble que l'anastomose coloanale donne de bons résultats du point de vue oncologique avec conservation d'une fonction sphinctérienne satisfaisante, même chez le patient âgé (plus de 62 ans).

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Presented at the Société Internationale de Chirurgie in Toronto, Ontario, Canada, September, 1989.     

Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma

In neuroblastoma, high levels of mRNA for p14h ^trkA and p75 ^LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140 ^trkA and ME20.4 anti-p75 ^LNGFR mAbs. Although weak, positiveimmunostaining was found in 9 of 28 tumors for p140 ^trkA and in 5 of 28 tumors for p75 ^LNGFR . As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140 ^trkA (p < 0.05) and 71% (20 of 28 cases) for p75 ^LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.     

Early-onset encephalomyopathy associated with tissue-specific mitochondrial DNA depletion: A morphological,biochemical and molecular-genetic study

A male infant, born from consanguineous parents, suffered from birth with a progressive neuromuscular disorder characterized by psychomotor delay, hypotonia, muscle weakness and wasting, deep-tendon areflexia and spastic posture. High levels of lactic acid in blood and cerebrospinal fluid suggested a mitochondrial respiratory chain defect. Muscle biopsy revealed raggedred and cytochromec oxidase-negative fibres, lipid accumulation and dystrophic changes. Multiple defects of respiratory complexes were detected in muscle homogenate, but cultured fibroblasts, myoblasts and myotubes were normal. Southern blot analysis showed markedly reduced levels of mitochondrial DNA (mtDNA) in muscle, while lymphocytes, fibroblasts and muscle precursor cells were normal. Neither depletion of mtDNA nor abnormalities of the respiratory complexes were observed in innervated muscle fibres cultured for as long as 4 months. No mutations were observed in two candidate nuclear genes,mtTFA andmtSSB, retro-transcribed, amplified and sequenced from the proband's mRNA. Sequence analysis of the mtDNA D-loop and of the origin of replication of the mtDNA light strand failed to identify potentially pathogenic mutations of these replicative elements in the proband's muscle mtDNA. Our findings indicate that mtDNA depletion is due to a nuclear encoded gene and suggest that the abnormality underlying defective mtDNA propagation must occur after muscle differentiation in vivo.     

The effect of accident mechanisms and initial findings on the long-term course of whiplash injury

The aim of this study was to assess the relationships between accident mechanisms as well as initial findings and the long-term course of whiplash injury. A representative sample of 117 consecutive patients referred by primary care physicians was followed-up over 12 months. Fractures or dislocations of the cervical spine, head trauma and pre-existing neurological disorders were exclusion criteria. The interval between the accident and the baseline examination was 7.4 days (SD 4.2 days). Assessment included accident features (e.g. passenger position in the car, head restraint, head position, type of collision), initial symptoms (e.g. intensity and onset of pain, symptoms of neurological dysfunction, multiple symptom score), and signs (restricted neck movement, neurological deficits). At the 1-year examination, patients were divided into an asymptomatic and a symptomatic group and were compared with respect to accident features and baseline findings. Twenty-four percent of patients were still symptomatic after 1 year. Analysing accident mechanisms separately, rotated or inclined head position was the primary feature related to symptom persistence (P=0.005). The symptomatic group scored higher at baseline on the multiple symptom rating (P=0.004) and had a higher incidence of initial headache (P=0.004) and neurological symptoms (P=0.008) together with a higher intensity of headache (P=0.0002) and neck pain (P=0.0009). The following set of initial variables predicted persistence of symptoms at 1 year (logistic regression): intensity of neck pain (P=0.001) and headache (P=0.009), rotated or inclined head position (P=0.02), unpreparedness at the time of impact (P=0.01) and car stationary when hit (P=0.01). In conclusion, accident mechanisms and initial findings suggestive of more severe injury were significantly related to long-term persistence of symptoms after whiplash injury.This study was supported by the Swiss National Science Foundation (project number: 3.883-0.88) and the Swiss Accident Insurance Company (Schweizerische Unfallversicherungsanstalt), Berne     

Identification of the central vestibular projections in man: a positron emission tomography activation study

The cerebral representation of space depends on the integration of many different sensory inputs. The vestibular system provides one such input and its dysfunction can cause profound spatial disorientation. Using positron emission tomography (PET), we measured regional cerebral perfusion with various vestibular stimulations to map central vestibular projections and to investigate the cerebral basis of spatial disorientation. We showed that the temporoparietal cortex, the insula, the putamen, and the anterior cingulate cortex are the cerebral projections of the vestibular system in man and that the spatial disorientation caused by unilateral vestibular stimulation is associated with their asymmetric activation.     

High-frequency ultrasound examination of the wrist and hand

High-frequency ultrasound (US) is an efficient, rapid and inexpensive altenative to magnetic resonance imaging (MRI) for investigation of diseases in the soft tissues of the wrist and hand. US allows detection of foreign bodies and the reliable identification of a variety of traumatic lesions affecting tendons, annular pulleys, ligaments, vessels and nerves. Inflammatory diseases of tendons, including acute and chronic tenosynovitis and some degenerative conditions in the wrist and hand, can also be diagnosed. In entrapment neuropathies, US is able to identify nerve shape changes and possible extrinsic space-occupying lesions that may cause nerve compression within the tunnels. In patients with localized swelling of the hand or wrist, US is able to assess the presence of an expansile lesion and to characterize its nature in most cases. The objective of this article is to review the main findings and the primary indications of US in the investigation of disorders of the hand and wrist. Received: 10 September 1998 Accepted: 24 November 1998     

Mesenteric cystic neoformations: Report of two cases

(Received for publication on Apr. 28, 1997; accepted on May 15, 1998)