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PubMed1997

A randomized, placebo-controlled study of oral cimetidine as an immunopotentiator of parenteral immunization with a group B meningococcal vaccine.

Cimetidine (CIM) is an H2-receptor antagonist with a long history of clinical use in peptic ulcer disease. In addition to its inhibitory effect upon gastric acid secretion, CIM can also block histamine-mediated immunosuppression by inhibiting H2 receptors on suppressor T cells. CIM results in immunoaugmentation of both cellular and humoral immunity by this mechanism and has been used clinically in the treatment of chronic infectious and neoplastic diseases. We postulated that orally administered CIM, like an adjuvant, could augment the immunologic response to a parenteral vaccine. To test this hypothesis, a randomized placebo (PLB)-controlled, double-blinded study in 14 healthy volunteers was performed using a Group B meningococcal outer membrane protein (OMP) vaccine administered twice, 6 weeks apart. Volunteers were randomized within pairs defined by their screening OMP antibody titers to receive either CIM or PLB which was administered for 5 days, beginning 2 days before each of the two immunizations. All 14 volunteers completed the study with excellent compliance. Sera were tested for anti-OMP and bactericidal antibodies. The groups were comparable in terms of gender distribution, age and baseline anti-OMP titers. Reactogenicity to the vaccine was mild and comparable between groups. There was little effect of CIM (over PLB) on anti-OMP or functional bactericidal antibody levels over time. Geometric means of maximum OMP antibody increase over baseline was 3.3-fold (95% CI: 1.8-6.3) for CIM and 2.4 for PLB (CI: 1.6-3.7). CIM had a corresponding 3.9-fold increase (CI: 1.9-8.3) in bactericidal antibody level compared to 2.2 for PLB (CI: 1.4-3.4). We conclude that oral CIM was not effective as an immunopotentiator of immunization with this group B meningococcal vaccine.

Adjuvants, Immunologic↗
PubMed1986

Analyses of oviposition times and intervals in a wide range of layer flocks under normal and continuous lighting regimes.

Distributions of oviposition times and intra-clutch oviposition intervals in continuous light (CL) and normal light (NL) environments were studied in 39 populations of 27 different genotypes. The populations showed a range of mean intervals from 23.1 to 27.6 h in CL, arising from the history of selection directly on interval in some populations. The data were analysed to infer empirical relations of descriptive statistics of the distribution to each other and to rate of lay to 301 d of age (PRL). In NL, as the mean intra-clutch interval decreased, more intervals tended to accumulate against the barrier of 24 h imposed by the light-dark cycle and the variability of intervals declined rapidly. Similar, but less striking, relations were found in CL above a mean interval of about 24 h. Under CL, the mean intra-clutch interval (CIM) decreased beneath 24 h and the variability of intervals tended to show a steep increase. The rate of lay to 301 d of age increased linearly at a rate of 6.3% for each hour by which CIM decreased to about 24 h, but no further below that level. Oviposition time in NL was advanced with a decrease in CIM, apparently in two linear phases of differing slopes, perhaps reflecting different physiological bases of the change. The degree of entrainment in NL, measured by the proportion of eggs laid in the model 8 h, increased with reduction of CIM. The distribution of oviposition times in CL showed a great deal of variation among the populations and departed significantly (P less than 0.05) from the uniform rectangular distribution, in all but three populations. The proportion of eggs laid in the modal 8 h of the day, suggested as an indicator of sensitivity to uncontrolled timing cues in CL, was positively correlated with CIM. Free-running periods were estimated for individual pullets from sequences of oviposition times in CL. The mean period for a population declined linearly with CIM, but only when CIM had decreased below about 25.75 h, suggesting that the period of endogenous circadian rhythm might have been altered in some populations with low CIM's. The proportion of eggs laid in the modal 8 h of the free-running period, perhaps an indicator for regularity of the circadian rhythm, was negatively correlated with CIM.

Animals↗
PubMed2000

Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia.

BACKGROUND: Biopsy specimens obtained from the gastro-oesophageal junction can reveal intestinal metaplasia in patients presenting for routine upper endoscopy. The site of biopsy may play a critical role in determining the dysplasia risk of a patient. AIMS: To evaluate prospectively the dysplasia risk in patients with intestinal metaplasia of the distal oesophagus or within the gastric cardia. METHODS: Patients with short segment Barrett's oesophagus (SSBO) and cardia intestinal metaplasia (CIM) were followed prospectively. RESULTS: 177 patients with SSBO were identified (mean age 62 years, range 38-82; 91% whites). Twenty prevalence cases of dysplasia in SSBO were detected: 17 low grade dysplasia (LGD), three high grade dysplasia (HGD). Seventy six patients with CIM were identified (mean age 67 years, range 37-81; 81% whites). A single prevalence case of LGD in CIM was detected. During follow up of 78 SSBO and 34 CIM patients, dysplasia developed in nine (seven LGD, two HGD) with SSBO and in one (LGD) with CIM. There were significant differences between the two groups with respect to age, ethnicity, dysplasia prevalence, and incidence. Time to dysplasia progression was significantly longer in CIM compared with SSBO patients. Of the five patients with SSBO and HGD, one developed adenocarcinoma of the oesophagus on follow up. No HGD or cancers have been detected over this time period in CIM patients. CONCLUSIONS: The dysplasia risk is significantly greater in SSBO than in CIM patients, indicating two potentially different clinical processes. Future studies should separate SSBO from CIM in order to enhance the understanding of the pathophysiology and malignant potential of each entity.

Adenocarcinoma↗
PubMed1998

Effect of combined fenthion and cimetidine use in rats on lethality, blood cholinesterase activities, and serum cholinesterase isoenzymes.

H2-receptor antagonists inhibit cholinesterase (ChE) activity. We examined perturbations in ChE isoenzyme patterns and ChE activities of rats from the combined effects of fenthion (FEN) and cimetidine (CIM). Sixty-four female Sprague-Dawley rats were divided into 8 groups. Four rat groups were given FEN or gum arabic solution and each group divided into 2 small groups according to the CIM or gum arabic administration. FEN was administered po at 12.3 mg/kg (1/20 LD50) or 24.5 mg/kg (1/10 LD50) for 14 days or 49 mg/kg (1/5 LD50) every 4 days. CIM was given po at 1,500 mg/kg from days 7 to 13. Samples were collected 3 h after CIM administration on days 8 and 13. CIM did not influence ChE isoenzyme patterns or ChE activity. FEN inhibited both the ChE isoenzyme patterns and ChE activities without producing clinical signs. Although 1 rat in the 12.5 mg FEN/kg + CIM group died on day 10, all rats in other FEN (24.5 mg/kg or 49 mg/kg) + CIM groups died on days 8-10. Differences in suppression of ChE isoenzyme patterns were detectable between the FEN-dosed and FEN + CIM-dosed groups. There were no differences in ChE activities between the FEN-dosed and FEN + CIM-dosed groups. The i.p. administration of 500 mg CIM/kg (LD50) did not suppress ChE activities.

Animals↗
PubMed1988

Enhancement by cimetidine of chemotactic peptide-stimulated ATP release and chemiluminescence in human neutrophils.

As determined by luciferase-luciferin, we recently found that the H2-blocker CIM considerably increased the ATP release from fMLP-stimulated PMN. This observation correlates well with our previous [1] regarding the enhancement of superoxide output (chemiluminescence) in in human neutrophils. by CIM plus fMLP. In order to compare the ATP release from PMN of different donors, a standard procedure has been developed consisting of the determination of the ATP present initially in the cell suspension (without stimulation), ATP release after stimulation with fMLP, and ATP release in the presence of CIM plus fMLP. The whole ATP content per neutrophil was determined after ultrasonication of the cells as well. The mean value of the initially present ATP was 0.45 x 10(-17) mol/cell in the suspension. Stimulation with fMLP plus CIM yielded within 5-10 minutes considerably higher ATP amounts than fMLP alone. The corresponding and statistically significantly different mean values were 2.46 x 10(-17) mol/PMN (s.d. = 1.047) and 1.38 x 10(-17) mol/PMN (s.d. = 0.55), respectively. The whole ATP per neutrophil was found to be 1.22 x 10(-15) mol (mean; s.d. = 0.60) and thus, the stimulation with CIM plus fMLP released about 2.0 per cent, with fMLP alone about 1.0 per cent of the whole ATP. CIM without fMLP did not enhanced the ATP release during the reaction time applied. On the other hand, fMLP-stimulated, lucigenin-amplified chemiluminescence determinations were carried out in the presence of CIM as well; contrarily to our previous method, CIM was dissolved in PBS without DMSO, because DMSO inhibited the chemiluminescence slightly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed2004

The incidence of inguinal complications after ventriculoperitoneal shunt for hydrocephalus.

AIM: This study outlines the incidence of acquired clinical inguinal manifestations (CIM) in infants undergoing ventriculoperitoneal (VP) shunt procedures, and the possible underlying mechanisms in the development of these pathologies. MATERIAL AND METHODS: The charts of children who had undergone VP shunt procedures for hydrocephalus between 1992 and 2002 were reviewed. All patients were contacted by a telephone interview, and they were invited to be examined in the outpatient clinic of paediatric surgery for the development of groin manifestation. RESULTS: Eighty-eight patients responded to the inquiry. Twenty-one (23.8%) patients developed a CIM. Three of them were premature infants. The mean interval between the shunt procedure and the diagnosis of CIM was 5.3 months (20 days to 48 months). Nineteen of the patients who developed a CIM were in the 0- to 12-month age group when the VP shunt procedures were initially performed. Ten CIM occurred on the right (47%), 7 on the left (33%) and 4 were bilateral (20%). The rate of bilateral patency as an operative finding was 76%. There was one recurrence (4.8%). CONCLUSION: The younger the age at which the VP shunt was performed, the higher the incidence of CIM. Bilateral manifestations were higher than in the normal population. Increased intra-abdominal pressure by accumulation of fluid in combination with the high patency rate of processus vaginalis possibly plays a role in the development of CIM in VP shunt patients. Bilateral repair should be considered even when CIM is unilateral. Special care should be given to repair procedures since the recurrence rate is relatively high.

Child, Preschool↗
PubMed1993

Modulation of the automaticity by histamine and cimetidine in rabbit sino-atrial node cells.

1. Effects of histamine (HIS) and cimetidine (CIM) on the spontaneous action potentials and ionic currents in rabbit sino-atrial node cells were investigated. 2. HIS accelerated the sinus rate at 10 mumol/l, and shortened the action potential duration (APD) at 100 mumol/l, significantly. The positive effects were blocked by CIM (100 mumol/l), but not by diphenhydramine (DPH, 1 mumol/l). HIS (100 mumol/l) elicited a dysrhythmia in 4 out of 10 preparations. Addition of acetylcholine (ACh) (1 mumol/l) depressed the HIS-induced effects, but dysrhythmia occurred in 5 of 10 preparations. 3. CIM (100 mumol/l) caused a negative chronotropic effect. The APD was prolonged, and the Vmax was decreased. Addition of pindolol (0.1 mumol/l) potentiated the depressions. CIM (3 mmol/l) caused a sinus arrest in 3 out of 7 preparations. 4. In voltage-clamp experiments, HIS (100 mumol/l) enhanced the slow inward current (Isi). The delayed rectifying K+ current (IK) and hyperpolarization-activated inward current (Ih) were also increased. The enhancement was inhibited by CIM (100 mumol/l), but not by DPH (1 mumol/l). CIM (100 mumol/l) alone depressed Isi, IK and Ih. Pindolol (0.1 mumol/l) potentiated the CIM-induced depressions significantly. 5. These results suggest that HIS and CIM would modulate the ionic currents mediated through H2-receptors, and that HIS possesses arrhythmogenic action (probably by cAMP accumulation), which is potentiated by ACh.

Action Potentials↗
PubMed1984

Prevention of radiation emesis in dogs by combinations of drugs.

Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis. Cim was chosen as an H2 antihistamine, Pro as an H1 antihistamine, and Thi as a phenothiazine derivative dopamine blocker. Doses were: 167 mg/m2 i.v. for Cim; 13.9 mg/m2 i.m. for Pro; and 5.6 mg/m2 i.m. for Thi. These doses were calculated on a mg/m2 basis to approximate doses for an average human (1.8 m2) of 300 mg Cim, 25 mg Pro, and 10 mg Thi. Exposure was to 60Co at 60 rad (midline) per min. The dogs were fed 0.4 kg canned dog food 1 hour before exposure, and injected with the appropriate drugs 30 minutes prior to exposure. Emesis onset times, number of episodes, and time to last episode were recorded. The radiation dose (midline tissue rad) to cause a 50% incidence of emesis (ED50) was calculated using an up-and-down procedure. The ED50 (95% confidence limits) were: 258 (212-315) for controls; 240 (151-380) for Cim; 313 (256-384) for Pro; 405 (319-514) for Thi; 334 (284-394) for Cim + Pro; 446 (365-546) for Cim + Thi; 347 (306-399) for Pro + Thi; and 478 (428-539) for Cim + Pro + Thi.

Animals↗
PubMed2006

Preparation of convection interaction media isobutyl disc monolithic column and its application to purification of secondary alcohol dehydrogenase and alcohol oxidase.

A convection interaction media (trade name CIM, BIA Separation, Ljubljana, Slovenia) isobutyl monolithic disc was prepared by incubating a CIM epoxy monolithic disc with isobutylamine, and it was then applied to the purification of secondary alcohol dehydrogenase (S-ADH) and primary alcohol oxidase (P-AOD). Both enzymes were adsorbed on this column and eluted with high purity. Thus, S-ADH was purified to an electrophoretically homogeneous state by four column chromatographies using CIM DEAE-8 and CIM C4-8 tube monolithic columns, blue-Sepharose column and CIM isobutyl disc monolithic column. P-AOD was also purified to an electrophoretically homogeneous state by three column chromatographies of CIM DEAE-8 tube, CIM C4-8 tube and CIM isobutyl disc columns.

Alcohol Dehydrogenase↗
PubMed2006

Characterization of reversible and pseudo-irreversible acetylcholinesterase inhibitors by means of an immobilized enzyme reactor.

The aim of the present study was the application of a human AChE-CIM-IMER (enzyme reactor containing acetylcholinesterase immobilized on a monolithic disk) for the rapid evaluation of the thermodynamic and kinetic constants, and the mechanism of action of new selected inhibitors. For this application, human recombinant AChE was covalently immobilized onto an ethylenediamine (EDA) monolithic Convective Interaction Media (CIM) disk and on-line studies were performed by inserting this IMER into a HPLC system. Short analysis time, absence of backpressure, low nonspecific matrix interactions and immediate recovery of enzyme activity were the best characteristics of this AChE-CIM-IMER. Mechanisms of action of selected reversible inhibitors (tacrine, donepezil, edrophonium, ambenonium) were evaluated by means of Lineweaver-Burk plot analysis. Analyses were performed on-line by injecting increasing concentrations of the tested inhibitor and substrate and by monitoring the product peak area. AChE-CIM-IMER kinetic parameters (Km(app) and vmax(app)) were derived as well as inhibitory constants (Ki(app)) of selected compounds. Moreover, noteworthy results were obtained in the application of the AChE-CIM-IMER to the characterization of the carbamoylation and decarbamoylation steps in pseudo-irreversible binding of carbamate derivatives (physostigmine and rivastigmine). AChE-CIM-IMER appeared to be a valid tool to determine simultaneously the kinetic constants in a reliable and fast mode. The obtained values were found in agreement with those obtained with the classical methods with the free enzyme. Furthermore, after inactivation by carbamates, activity could be fully recovered and the AChE-CIM-IMER could be reused for further studies. Results showed that the AChE-CIM-IMER is a valid tool not only for automated fast screening in the first phase of the drug discovery process but also for the finest characterization of the mode of action of new hit compounds with increased accuracy and reproducibility and with saving of time and materials.

Acetylcholinesterase↗
PubMed1998

H2 histaminergic control of inhibition of eating induced by intragastric NaCl in rats.

A role for endogenous histamine and histamine receptor subtypes in mediating the inhibition of eating induced by intragastric (i.g.) hypertonic NaCl was examined in adult male Sprague-Dawley rats surgically equipped with a chronic gastric catheter. The i.g. infusion of 2 mL 900 or 1,800 mOsm/kg of NaCl inhibited: 1) ingestion of pellets in rats eating after 24-h food deprivation; and 2) ingestion of cookies in rats eating without prior deprivation. The H1 receptor antagonists dexbrompheniramine (DXB; 1 mg/kg) and pyrilamine (PYR; 4 mg/kg) did not attenuate the inhibitory effects of i.g. 900 or 1,800 mOsm/kg of NaCl for rats eating pellets and for rats eating cookies. The H2 antagonists cimetidine (CIM; 16 mg/kg) and metiamide (MET; 16 mg/kg) attenuated the inhibitory effects of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cookies, but intracerebroventricular (i.c.v.) infusion (through a chronic indwelling cannula) of 100 microg of CIM did not mimic this effect of intraperitoneal (i.p.) CIM. The i.p. CIM failed to attenuate the inhibition of eating cookies produced by i.p. octapeptide of cholecystokinin (CCK-8; 3 microg/kg). The H3 antagonist thioperamide (TH; 10 mg/kg i.p.) and the H3 agonist R-alpha-methylhistamine (RAM; 3 mg/kg i.p.) did not alter the inhibitory effect of i.g. 1,800 mOsm/kg of NaCl for rats eating cookies. Combined treatments of systemic DXB plus CIM, and DXB plus CIM plus thioperamide (TH) did not reverse the inhibitory effects of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cookies. Finally, i.p. DXB, but not CIM, attenuated the ability of i.g. 900 mOsm/kg of NaCl to increase water intake; conversely, i.p. CIM, but not DXB, attenuated the ability of i.g. 900 mOsm/kg of NaCl to inhibit eating of cookies. These findings demonstrate a double dissociation of effects upon ingestive behavior: H1, but not H2, antagonism attenuates the effect of i.g. hypertonic NaCl on water intake, whereas H2, but not H1, antagonism attenuates the inhibition of eating produced by i.g. hypertonic NaCl. These results demonstrate that different subtypes of peripheral and/or central histamine receptors contribute to different behavioral consequences of postprandial gastrointestinal osmotic loads in rats.

Animals↗
PubMed2006

Impact of malnutrition-inflammation on the association between homocysteine and mortality.

Whether high total serum homocysteine levels (tHcy) contribute to increase mortality or offer a survival advantage in chronic hemodialysis patients remains controversial. We conducted a prospective study to determine the impact of tHcy on survival in this population with special respect to chronic inflammation-malnutrition state (CIMS). In this prospective study, 459 hemodialysis patients from 10 dialysis centers located in two regions of France were included. A number of baseline parameters were measured including tHcy and markers of CIMS. Over a mean follow-up period of 54 months, 219 deaths (47.7%) occurred, of which 114 (52%) were of cardiovascular (CV) origin. tHcy of equal to or greater than 30 micromol/l was associated with a higher risk of all-cause mortality in patients without CIMS (hazard ratio (HR): 1.55 (confidence interval (CI): 1.12-4.72)), but not in overall dialysis population or those with CIMS. When only CV mortality was considered, tHcy of equal to or greater than 30 micromol/l was associated with a higher risk in patients without (CIMS HR: 1.91 (CI: 1.23-3.23)), but not in those with CIMS. Hyperhomocysteinemia is a strong risk factor for all-cause and CV mortality in hemodialysis patients who do not present CIMS. This association might be masked in patients with CIMS.

Aged↗
PubMed2005

Understanding critical illness myopathy: approaching the pathomechanism.

Myopathies occurring in critically ill patients have gained increasing interest during the past years. For the patient, they represent a crucial factor for prolonged intensive care unit treatment and secondary complications. Critical illness myopathies (CIMs) seem to be related to various pathogenic factors. Among those, the septic inflammatory response syndrome seems to play a major role. It has been suggested that, similar to sepsis-related multiorgan failure, CIM might be considered a failure of the organ muscle. Muscle function might be impaired by proposed "myotoxic" humoral factors. These could be endogenously produced during the innate immune response to sepsis. This article follows up recent evidence for such active fractions in the blood serum of CIM patients. To explain muscle weakness in CIM, serum fractions acutely modified membrane excitability and subcellular Ca2+ regulation in an animal model. From the differential serum effects, early-phase CIM seems to involve a reduction in the overall force generation in muscle but also a compensation by the membrane, increasing the excitability. Different animal models will help to elucidate the underlying mechanisms accounting for the specific proteolytic activities found in different forms of CIM. CIM represents a systemic rather than a local disorder. Humoral factors might initiate the local reaction of skeletal muscle clinically seen as muscle weakness, altered excitability, and proteolysis of contractile proteins. Establishing the interactions in the excitation-contraction cascade in CIM is a challenging task, not only to clarify its pathomechanism but also to deduce clinical interventions.

Animals↗
PubMed2004

Cytokeratin 7/20 and MUC1, 2, 5AC, and 6 expression patterns in Barrett's esophagus and intestinal metaplasia of the stomach: intestinal metaplasia of the cardia is related to Barrett's esophagus.

Intestinal metaplasia (IM) in endoscopic biopsies obtained from close to the gastroesophageal junction may represent IM of the cardia (CIM) or Barrett's esophagus (BE), which have different malignant potentials despite similar morphology. This study compared cytokeratin (CK) 7/20 and mucin (MUC1, 2, 5AC, and 6) immunopatterns in biopsies from BE (n = 41), CIM (n = 35), and antral gastric IM (AIM, n = 37) to evaluate their roles as diagnostic aids. CK7 and CK20 expression was described as absent, patchy (superficial and deep), continuous superficial only, continuous deep only, and diffuse. Eleven different combinations of CK7/20 expression were seen. Since CK20 staining was positive in all cases, four main patterns were defined on the basis of the observed CK7 staining as 1, absent; 2, patchy (superficial and/or deep); 3, diffuse; and 4, continuous superficial only. Overall CK7 positivity (regardless of pattern) was higher in BE and CIM than in AIM. CK patterns 3 and 4 were also higher in BE and CIM than in AIM. For either pattern 3 or 4, the positive and negative predictive values for BE versus AIM were 95% and 67%, respectively. MUC1 was rarely expressed in BE and CIM compared with AIM, whereas the opposite was noted for MUC5AC expression. MUC2 and MUC6 expression was similar in all locations. In conclusion, diffuse or continuous superficial CK7 staining is highly characteristic of BE and CIM and contrasts with AIM. It is, however, not very sensitive. CK20 profiles have no added value. Mucin expression also differs between BE and CIM versus AIM, but the specificity of any pattern is insufficient for distinction in individual cases. Importantly, CK and MUC expression patterns in BE and CIM are virtually indistinguishable, limiting their use in this differential and raising the question of whether they are biologically related.

Barrett Esophagus↗
PubMed2004

Relative contribution of OAT and OCT transporters to organic electrolyte transport in rabbit proximal tubule.

We compared the characteristics of several cloned rabbit organic electrolyte (OE) transporters expressed in cultured cells with their behavior in intact rabbit renal proximal tubules (RPT) to determine the contribution of each to basolateral uptake of the weak acid ochratoxin A (OTA) and the weak base cimetidine (CIM). The activity of organic anion transporters OAT1 and OAT3 proved to be distinguishable because OAT1 had a high affinity for PAH (K(t) of 20 microM) and did not support estrone sulfate (ES) transport, whereas OAT3 had a high affinity for ES (K(t) of 4.5 microM) and a weak interaction with PAH (IC(50) > 1 mM). In contrast, both transporters robustly accumulated OTA. Intact RPT also accumulated OTA, with OAT1 and OAT3 each responsible for approximately 50%: ES and PAH each reduced uptake by approximately 50%, and the combination of the two eliminated mediated OTA uptake. The weak base CIM was transported by OAT3 (K(t) of 80 microM) and OCT2 (K(t) of 2 microM); OCT1 had a comparatively low affinity for CIM, and CIM uptake by OAT1 was equivocal. Intact RPT accumulated CIM, with TEA and ES reducing CIM uptake by 20 and 75%, respectively, suggesting that OAT3 plays a quantitatively more significant role in CIM uptake in the early proximal tubule than OCT1/2. In single S2 segments of RPT, ES and TEA each blocked approximately 50% of CIM uptake. Thus the fractional contribution of different OE transporters to renal secretion is influenced by their affinity for substrate and relative expression level in RPT.

Animals↗
PubMed2003

Children with growth hormone deficiency and Chiari I malformation: a morphometric analysis of the posterior cranial fossa.

OBJECTIVE: The posterior fossa (PF) has been found to be small in various forms of Chiari malformation. Explanations involving a connection between growth hormone deficiency (GHD) and Chiari I malformation (CIM) have been proposed. However, to date, no quantitative analysis of the PF of patients with CIM and GHD has been performed. Our study was performed to determine the geometry of the PF in children with GHD and CIM. METHODS: Morphometric analysis of the PF was performed in 10 children with GHD and CIM (group 1), 20 children with GHD and no CIM (group 2) and 50 controls. RESULTS: PF volumes for group 1 ranged from 128 to 259 +/- 33 ml, and for group 2, they ranged from 115 to 186.2 +/- 25.4 ml. Lengths of the foramen magnum for groups 1 and 2 had means of 36 and 38 mm, respectively. The mean basiocciput length and tentorial angle for groups 1 and 2 were 20 and 19 mm and 89 and 87.5 degrees, respectively. CONCLUSIONS: We have determined that children with GHD with or without CIM have no significant difference in their PF volume compared to controls. However, our data demonstrate significant underdevelopment of portions of the bony PF in both patients with GHD alone and in patients with GHD and CIM. Tentorial angles were elevated in noncontrol groups. We propose that this association is not due to an increased rate of 'midline' defects seen in GHD but rather a structurally distorted PF that is not capacious enough to house the entire developing rhombencephalon. These data will hopefully aid in the further understanding of the pathophysiology of CIM.

Adolescent↗
PubMed2000

Does the application of constraint-induced movement therapy during acute rehabilitation reduce arm impairment after ischemic stroke?

BACKGROUND AND PURPOSE: Motor dysfunction after unilateral deafferentation in primates can be overcome by restraining the unaffected limb. We asked whether a constraint-induced movement (CIM) program could be implemented within 2 weeks after stroke and whether CIM is more effective than traditional upper-extremity (UE) therapies during this period. METHODS: Twenty-three persons were enrolled in a pilot randomized, controlled trial that compared CIM with traditional therapies. A blinded observer rated the primary end point, the Action Research Arm Test (ARA). Inclusion criteria were the following: ischemic stroke within 14 days, persistent hemiparesis, evidence of preserved cognitive function, and presence of a protective motor response. Differences between the groups were compared by using Student's t tests, ANCOVA, and Mann-Whitney U: tests. RESULTS: Twenty subjects completed the 14-day treatment. Two adverse outcomes, a recurrent stroke and a death, occurred in the traditional group; 1 CIM subject met rehabilitation goals and was discharged before completing 14 inpatient days. The CIM treatment group had significantly higher scores on total ARA and pinch subscale scores (P:<0.05). Differences in the mean ARA grip, grasp, and gross movement subscale scores did not reach statistical significance. UE activities of daily living performance was not significantly different between groups, and no subject withdrew because of pain or frustration. CONCLUSIONS: A clinical trial of CIM therapy during acute rehabilitation is feasible. CIM was associated with less arm impairment at the end of treatment. Long-term studies are needed to determine whether CIM early after stroke is superior to traditional therapies.

Aged↗
PubMed1983

Are fasting-induced effects on thyrotropin and prolactin secretion mediated by dopamine?

To investigate whether total caloric deprivation influences TSH and/or PRL responsiveness, seven healthy volunteers fasted overnight (8 h) and were injected iv with a small dose (25 micrograms) of TRH and 30 min later with 40 mg cimetidine (CIM). This combined TRH-CIM test was repeated in the same individuals after a fasting period of 56 h. The TRH-stimulated mean maximal TSH increment fell from 5.1 +/- 1.2 to 1.2 +/- 0.6 microU/ml (P less than 0.01) during fasting. In contrast, both the TRH- and CIM-induced PRL responses were unaffected. To exclude methodologic errors on this reduced TSH responsiveness, an additional four normal subjects fasted for 56 h and then were given TRH alone. Two days later the TRH test was repeated after a fasting period of only 8 h. This experimental design also resulted in a significantly lower TSH response after the longer fasting period than after the shorter period, thus demonstrating that prolonged fasting inhibits TSH responsiveness regardless of whether the starvation period precedes or follows the TRH injection, and regardless of whether the pituitary thyrotrophs are stimulated with TRH plus CIM, or with TRH alone. In an additional seven healthy subjects injected with TRH plus CIM before and after a fasting period of 56 h, a dopamine D-2 receptor blocking agent, metoclopramide (MET), was given orally 90 min before the second TRH-CIM load. This priming with MET failed to restore normal TSH responsiveness in the fasting subjects, thus indicating that the suppressed TSH secretion could not have been mediated through dopamine D-2 receptors. However, since oral pretreatment with MET completely abolished the CIM-elicited PRL response in the fasting subjects, it is reasonable to assume that CIM stimulates PRL release via a reduced dopaminergic inhibition of the pituitary lactotrophs.

Adult↗