Results of thyroidectomies according to general surgeons and otolaryngologist and cervico faciale surgeons at the general Hospital of Reference of Niamey, what differences in the protocols of management?

OBJECTIVE: To evaluate the surgical management of thyroid pathologies at the Reference General Hospital. METHODS: This was a retro-prospective study over 4 years 6 months carried out in the departments of General and Digestive Surgery (GDS) and Otorhinolaryngology and Cervico Facial Surgery (ORL/FCS). It involved 182 patients who underwent thyroid surgery. RESULTS: A frequency of thyroidectomy of 9.46% was found. Females predominated with a sex ratio of 0.1. The average age of patients was 42.85 years, a standard deviation 12.80. 84.06% of patients had consulted for anterior cervical mass. EU-TIRADS score 3 represented 7,14% of cases. Heteromultinodular goiter was the main indication for thyroid surgery (59.34%). Total thyroidectomy was the most commonly performed gesture in general surgery in 88,23% (n = 105), in Otorhinolaryngology, it was in the same proportion as lobo-isthmectomy at 47.61% (n = 30). The first route was video-assisted thyroidectomy 2.2% (n = 4). The recurrent laryngeal nerve was dissected and seen in 159 cases (87.36%) and parathyroid glands were also seen and preserved in 58.24% of cases (n = 106). In immediate postoperative surgery, the main complications were unilateral recurrent paralysis with dysphonia in 3.3% (n = 6) and compressive hematoma in 2.2% (n = 4). No deaths had been recorded. CONCLUSION: Total thyroidectomy was the most performed procedure in department of General and Digestive Surgery. Routine oral calcium and vitamin D supplementation in the general surgery ward, reduces the occurrence of hypocalcemia after total thyroidectomy and allows a safe and early exit. Standardizing protocols will further reduce complications.

Fc-Gamma Receptor Polymorphisms Predispose Patients to Infectious Complications After Liver Transplantation.

We investigated the impact of polymorphisms in host innate immunoregulatory genes on the development of infectious complications after liver transplantation (LT). The single-nucleotide polymorphisms (SNPs) of C1QA [276A/G], FCGR2A [131H/R], and FCGR3A [158F/V], genes encoding the Fc gamma receptor (FcγR), were analyzed in 89 living donor LT recipients in relation to the occurrences of postoperative infectious complications within 30 days after LT. Consistent with a lower affinity of the isoform encoded by FCGR3A [158F] to both IgG1 and IgG3, a significantly higher incidence of bloodstream infections (BSI) was observed in the FCGR3A [158F/V or F/F] than in the FCGR3A [158V/V] individuals. The combination of FCGR2A and FCGR3A SNPs further stratified the incidence of BSI, regardless of C1QA SNP. The predominant causative pathogen of BSI in the FCGR3A [158F/F or F/V] patients was gram-positive cocci (73.3%), of which one third was methicillin-resistant Staphylococcus aureus. No differences were observed in the incidence of fungal infections or in cytomegalovirus infections with respect to the three gene polymorphisms. Our findings indicate that FcγR SNPs are predisposing factors for BSI and can predict mortality after LT. This study provides a foundation for further prospective studies on a larger scale.

Pharmacokinetics, efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: pilot study.

The aim of this study was to evaluate the pharmacokinetic profile of daclatasvir (DCV) and asunaprevir (ASV) dual therapy in haemodialysis patients infected with hepatitis C virus (HCV). Eighteen haemodialysis patients and 54 patients with normal renal function were treated with DCV and ASV dual therapy for 24 weeks. We evaluated the pharmacokinetic profiles of DCV and ASV and examined the rate of sustained virological response 12 weeks after the end of treatment (SVR12 ) and incidence of adverse events during treatment of haemodialysis patients infected with chronic HCV genotype 1 infection. To adjust for potential differences in baseline characteristics between haemodialysis patients and patients with normal renal function, we used propensity scores case-control matching methods. Area under the plasma concentration time curve from 0 to 6 h (AUC0-6 h ) of DCV was slightly lower in haemodialysis patients than in patients with normal renal function (P > 0.6). AUC0-6 h of ASV was significantly lower in haemodialysis patients (P = 0.012). SVR12 rates were 100% (18/18) for haemodialysis and 96.2% (52/54) for patients with normal renal function. Changes in mean log10 HCV RNA levels and viral response were higher in haemodialysis patients compared to patients with normal renal function. No discontinuations due to adverse events occurred. In conclusion, DCV and ASV dual therapy for HCV infection is effective and safe with similar results in haemodialysis patients compared to patients with normal renal function.

The dipeptidyl peptidase-4 inhibitor vildagliptin has the capacity to repair ß-cell dysfunction and insulin resistance.

The aim of the present study was to determine whether the dipeptidyl peptidase (DPP)-4 inhibitor could repair pancreatic ß-cell dysfunction and insulin resistance. Ten subjects with type 2 diabetes who had never received DPP-4 inhibitor treatment were enrolled in the study. Just before and 3 months after twice-daily administration of vildagliptin (50 mg tablets), insulin secretion and insulin sensitivity were estimated using 2-compartment model analysis of C-peptide kinetics and insulin-modified minimal model parameters, respectively. The first-phase insulin secretion (CS1) was determined as the sum of the C-peptide secretion rate (CSR) from 0 to 5 min (normal range 6.8-18.5 ng/ml/min). The whole-body insulin sensitivity index (SI) was calculated using a minimal model software program (normal range 2.6-7.6×10(-4)/min/µU/ml). After vildagliptin treatment, reductions in mean (± SE) HbA1c were noted (43.28±1.53 vs. 40.98±1.77 mmol/mol; p=0.019). Vildagliptin treatment increased the area under the curve for the C peptide reactivity (CPR) (AUCCPR; 26.66±5.15 vs. 33.02±6.12 ng/ml · 20 min; p=0.003) and CS1 (0.80±0.20 vs. 1.35±0.38 ng/ml/min; p=0.037) in response to an intravenous glucose load. -Vildagliptin treatment significantly increased SI (0.46±0.27 vs. 1.21±0.48×10(-4)/min/µU/ml; p=0.037). The long-term administration of vildagliptin improved CS1 and Si suggesting that this drug has the capacity to repair impairments in pancreatic ß-cell function and insulin resistance in type 2 diabetes.

Effects of estrogen and progesterone on cerebrovascular responses to euoxic hypercapnia in women.

OBJECTIVES: To determine the cerebral blood flow response to step changes in end-tidal Pco(2) in premenopausal women (n = 10; mean age±standard deviation 27.0±6.4 years) during the follicular (FP), mid-cycle (MC) and luteal (LP) phases of the menstrual cycle. METHODS: Transcranial Doppler ultrasound was used to measure beat-by-beat averaged peak blood flow velocity (V(p)) in the middle cerebral artery in response to 20 min of euoxic hypercapnia (end-tidal PO(2) = 88 Torr; end-tidal PCO(2) = 7.0 Torr above resting values). The V(p) responses to euoxic hypercapnia were fitted to a simple mathematical model that included gain terms for the on (G(on)) and off (G(off)) responses, time constants for the on (τ(on)) and off (τ(off)) responses, baseline terms and a time delay (T(d)). RESULTS: Serum progesterone levels were significantly greater for LP compared to FP and MC (40.6±13.2 vs. 32.6±1.4 nmol/l (p < 0.001) and 8.8±3.8 nmol/l (p < 0.001), respectively). Serum estrogen concentrations were significantly lower in FP compared to MC and LP (150.9±51.2 vs. 506.5±220.5 pmol/l (p = 0.002) and 589.1±222.8 pmol/l (p < 0.001), respectively). Arterial PCO(2) was significantly greater in MC compared to LP (35.0±2.1 and 32.6±1.4 Torr, respectively; p = 0.02). There was a significant increase in G(off) during LP compared with FP and MC (3.38±0.68 vs. 2.79±0.82 cm s(-1) Torr(-1) (p = 0.021) and 2.74±0.90 (p = 0.018) cm s(-1) Torr2(1), respectively). Progesterone and the estrogen/progesterone ratio contributed to the observed differences in G(off). CONCLUSION: There is an increase in G(off) during LP that is explained, at least in part, by increases in serum progesterone and estrogen and a decrease in arterial PCO(2).

Plasma MMP-9 Levels as the Future Risk of Conversion to Dementia in ApoE4-Positive MCI Patients: Investigation Based on the Alzheimer's Disease Neuroimaging Initiative Database.

BACKGROUND: Matrix metalloproteinase 9 (MMP-9) has been reported to be correlated with declines in hippocampal volume and cognitive function in ApoE4-positive MCI patients. OBJECTIVES: The present study was aimed to investigate the effects of plasma matrix MMP-9 on the conversion risk between mild cognitive impairment (MCI) patients with and without ApoE4. DESIGN AND SETTING: Retrospective observational study using the data extracted from the Alzheimer's Disease Neuroimaging Initiative database. PARTICIPANTS: We included 211 ApoE4-positive MCI subjects (ApoE4+ MCI) and 184 ApoE4-negative MCI subjects (ApoE4- MCI). MEASUREMENTS: We obtained demographic and data including plasma MMP-9 levels at baseline and longitudinal changes in Clinical Dementia Rating (CDR) up to 15 years. We compared conversion rates between ApoE4+ MCI and ApoE4- MCI by the Log-rank test and calculated the hazard ratio (HR) for covariates including age, sex, educational attainment, drinking and smoking histories, medications, and plasma MMP-9 levels using a multiple Cox regression analysis of ApoE4+ MCI and ApoE4- MCI. RESULTS: No significant differences were observed in baseline plasma MMP-9 levels between ApoE4+ MCI and ApoE4- MCI. High plasma MMP-9 levels increased the conversion risk significantly more than low plasma MMP-9 levels (HR, 2.46 [95% CI, 1.31-4.48]) and middle plasma MMP-9 levels (HR, 1.67 [95% CI, 1.04-2.65]) in ApoE4+ MCI, but not in ApoE4- MCI. CONCLUSION: Plasma MMP-9 would be the risk of the future conversion to dementia in ApoE4+ MCI.

Plasmid DNA is released from nanosized acicular material surface by low molecular weight oligonucleotides: exogenous plasmid acquisition mechanism for penetration intermediates based on the Yoshida effect.

When a colloidal solution consisting of nanosized acicular material and bacterial cells is stimulated with sliding friction at the interface between the hydrogel and interface-forming material where the frictional coefficient increases rapidly, the nanosized acicular material accompanying the bacterial cells forms a penetration intermediate. This effect is known as the Yoshida effect in honor of its discoverer. Through the Yoshida effect, a novel property in which penetration intermediates incorporate exogenous plasmid DNA has been identified. This report proposes a possible mechanism for exogenous plasmid acquisition by penetration intermediates in the Yoshida effect. Escherichia coli cells, pUC18, and chrysotile were used as recipient cells, plasmid DNA, and nanosized acicular material, respectively. Even when repeatedly washing the mixture consisting of pUC18 and chrysotile, transformation efficiency by pUC18 was stable. Accordingly, pUC18 adsorbed onto chrysotile was introduced into recipient E. coli cells. At saturation, the amount of pUC18 adsorbed onto chrysotile was 0.8-1.2 microg/mg. To investigate whether pUC18 adsorbed on chrysotile is replicated by polymerase, polymerase chain reaction (PCR) was carried out with the chrysotile. Amplification of the beta-lactamase gene coded in pUC18, which was adsorbed onto chrysotile, was strongly inhibited. This suggests that DNA adsorbed onto chrysotile is not replicated in vivo. When we searched for substances to release pUC18 adsorbed onto chrysotile, we found that a 300-bp single- or double-stranded segment of DNA releases pUC18 from chrysotile. Competitive adsorption onto chrysotile between double-stranded DNA and pUC18 was then examined through the Yoshida effect. The 310- and 603-bp double-stranded nucleotides caused 50% competitive inhibition at the same molar ratio with pUC18. Hence, the adsorbed region of pUC18 is about 300 bp in length. As the culture period for recipient cells increases, transformation efficiency decreases while the expression levels of small RNA of 300-600 bp also decrease. These results suggest that pUC18 adsorbed onto chrysotile can be released by 300-bp small RNA, replicated by DNA polymerase, and transferred to daughter cells.

INJURIES OF BOKO HARAM INSURGENCY IN SOUTH-EAST NIGER REPUBLIC.

BACKGROUND: Currently, wounds of wars, terrorism and criminality are increasing and constitute major public health problem worldwide. AIM: To present the epidemiological, clinical and therapeutic characteristics of the wounds observed during the Boko Haram (BH) insurgency in the South-east of the Republic of Niger. METHODOLOGY: This was a cross-sectional study from December 2014 to December 2016 at Diffa Regional Hospital, Diffa, Niger of individuals whose injuries were as a result of Boko Haram insurgency. RESULTS: In the period of this study, 573 injuries from Boko Haram insurgency were managed at the Regional Hospital at Diffa. The majority, 513(89.5%), were males while females constituted 60(10.5%) with a male/female ratio of 8.55. The mean age was 30,94(SD24,91) years (range 1 to 97 years). Civilian victims accounted for 379 (66.1%) while Nigerien soldiers accounted for 160(27.9%) and 34 (5.9%) were Boko Haram fighters. Firearms and explosives accounted for injuries in 489 (85.3%) and 7(1.2%) of patients respectively; 42 (7.3%) suffered injuries from a variety of traditional weapons. Injuries to limbs accounted for 361(63%) of cases and polytrauma in 65(11.34%). The main surgical management included wound debridement in 409 (71.4%), external bone fixation in 38 (6.6%), laparotomy in 30 (5.2%), thoracic drainage in 27 (4.7%), and major limb amputations in 13 (2.3%) cases.Postoperative follow-up was uneventful in 460 (80.28%) of cases; there were 29 deaths, giving a mortality rate of 5.1%. Predictors of death after injuries of Boko Haram terrorism in this study included: being civilian patients (OR = 3.38 [1.15-9.85], p=0.018), injuries to head, neck, trunk or spine (OR 3.45[1.58-7.58], p= 0.001) or the presence of polytrauma on admission (OR = 17.30 [7.72-38.80], p<0.0001). CONCLUSION: This study has shown that injuries sustained in Boko Haram insurgency in Niger were mainly firearm injuries and injuries from the use of traditional weapons, affecting mostly young civilian males. The part of the body most commonly involved were the extremities, with mainly soft tissue injuries. Wound debridement was the commonest surgical procedure performed and the mortality rate was 5.1%. Predictors of mortality were being civilian patients, injuries of head, neck, trunk or spine and polytrauma. The ICRC has played a major role in strengthening our hospital for the task of caring for the victims, in terms of provision of material resources and in the further training of our personnel.

Sarcoidosis of the tongue: a case report.

A case of sarcoidosis involving the tongue is described in a 48-year-old Japanese man. A definite diagnosis of sarcoidosis was made for the clinical lesion and pathological examinations. Sarcoidosis is a multisystem granulomatous disease that may affect any organ. Sarcoidosis of the tongue is particularly rare.

Acute Graft Rejection and Formation of De Novo Donor-Specific Antibodies Triggered by Low Cyclosporine Levels and Interferon Therapy for Recurrent Hepatitis C Infection After Liver Transplantation: A Case Report.

BACKGROUND: We report a case of acute rejection of a liver graft, together with the occurrence of de novo donor-specific antibodies (DSAs), in a 53-year-old Japanese man who had undergone deceased-donor liver transplantation. METHODS: The graft rejection was triggered by low cyclosporine levels and pegylated interferon treatment for the recurrence of hepatitis C virus (HCV) infection 18 months after transplantation. Although the graft was ABO-compatible, pre-formed DSA B51 was detected; therefore, total plasma exchange was performed and intravenous rituximab (500 mg/body) was administered before transplantation. RESULTS: DSA was absent 6 months after transplantation. HCV recurrence was treated with pegylated interferon-α-2a. Renal function deteriorated with this anti-HCV therapy, with serum cyclosporine levels decreasing to 50 ng/mL. A rapid virologic response was achieved, but liver function deteriorated after 3 months of anti-HCV therapy, with histologic evidence of acute cellular rejection and formation of de novo DSAs. Anti-thymocyte globulin was administered for 5 days, which led to immediate improvement in liver function. However, renal function declined, warranting hemodialysis. The patient recovered 2 months after acute rejection, although de novo DSAs persisted. CONCLUSIONS: Careful immunologic monitoring may be required for patients receiving interferon therapy for HCV infection to maintain sufficient blood levels of immunosuppressive agents and to prevent acute liver graft rejection.

MELD and Child-Pugh Scores Are Related to Immune Status of Intrahepatic Natural Killer Cells in Liver Transplant Candidates.

BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation. The relationship between the clinical severity of liver disease and the phenotype of intrahepatic NK cells in these patients was also evaluated. To estimate the immunological responsiveness of intrahepatic NK cells, phenotypic enhancement after interleukin-2 stimulation was analyzed. RESULTS: Intrahepatic NK cells from patients with advanced liver failure exhibited down-regulated monomodal expression of NKp46, a major activating molecule. Notably, the expression level of NKp46 decreased depending on the severity of liver disease, Model for End-Stage Liver Disease score, and Child-Pugh score rather than the etiology. After in vitro recombinant interleukin-2 stimulation, the enhancement of expression of cytotoxic molecules, NKp44, and tumor necrosis factor-related apoptosis-inducing ligand was significantly impaired in intrahepatic NK cells from patients with liver failure, concurrently with decreased expression of CD122 and interleukin-2 receptor beta. CONCLUSIONS: Our results suggest that terminal deterioration of liver environments by chronic liver disease impairs the potential of local NK cells, depending on the severity of the deterioration. These influences of advanced liver failure on intrahepatic NK cells may be attributed to multicentric carcinogenesis in patients with liver failure.

Cerebral blood flow and metabolism during exercise.

During exercise regional cerebral blood flow (rCBF), as blood velocity in major cerebral arteries and also blood flow in the internal carotid artery increase, suggesting an increase in blood flow to a large part of the brain. Such an increase in CBF is independent of the concomitant increase in blood pressure but is modified by the alteration in arterial carbon dioxide tension (PaCO(2)). Also, the increase in middle cerebral artery mean blood velocity (MCA V(mean)) reported with exercise appears to depend on the ability to increase cardiac output (CO), as demonstrated in response to beta-1 blockade and in patients with cardiac insufficiency or atrial fibrillation.Near-infrared spectroscopy (NIRS) determined cerebral oxygenation supports the alterations in MCA V(mean) during exercise. Equally, the observation that the cerebrovascular CO(2)-reactivity appears to be smaller in the standing than in the sitting and especially in the supine position could relate to the progressively smaller CO. In contrast, during exercise "global" cerebral blood flow (gCBF), as determined by the Kety-Schmidt technique is regarded as being constant. One limitation of the Kety-Schmidt method for measuring CBF is that blood flow in the two internal jugular veins depends on the origin of drainage and it has not been defined which internal jugular venous flow is evaluated. Such a consideration is equally relevant for an evaluation of cerebral metabolism during exercise. While the regional cerebral uptake of oxygen (O(2)) increases during exercise, the global value is regarded as being constant. Yet, during high intensity exercise lactate is taken up by the brain and its O(2) uptake also increases. Furthermore, in the initial minutes of recovery immediately following exercise, brain glucose and O(2) uptake are elevated and lactate uptake remains high.A maintained substrate uptake by the brain after exercise suggests a role for brain glycogen in cerebral activation, but the fate of brain substrate uptake has not yet been determined.

Fragmentation of the beta-subunit of human chorionic gonadotropin produced by choriocarcinoma.

When human chorionic gonadotropin (hCG) was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions with dithiothreitol (DTT), a smaller weight material (CTP'), in addition to the beta-subunit, could be detected by Western blot analysis using antiserum for hCG beta-carboxy-terminal peptide (CTP). The CTP' band was much more apparent with urinary hCG from a patient with choriocarcinoma than with that from normal pregnant women. Second-dimensional electrophoresis of the choriocarcinoma hCG (c-hCG) after reduction with DTT indicated that the CTP', Mr 25,000, was released from the beta-subunit. The carbohydrate structure of the CTP' was analyzed by affinity with lectin-peroxidase on a nitrocellulose membrane. The CTP' did not interact with Concanavalin A, but exhibited strong interaction with both RCA120 and Arachis hypogaea after removal of sialic acid, indicating that it was released as a fragment containing an O-linked sugar chain as was found in the hCG beta carboxy-terminal portion. Western blot analysis using the antisera for hCG alpha, hCG beta, and hCG beta-CTP showed that the CTP' contains not only the carboxy-terminal portion but also a part of the internal (core) portion of the beta-subunit molecule. This dissociation of the c-hCG beta was further supported by the presence of a faster moving component (FMC) which may correspond to the NH2-terminal side counterpart. The desialylated FMC could be detected by Concanavalin A and RCA120 but not by Arachis hypogaea, indicating that it contains N-linked rather than O-linked sugar chains. The FMC does not contain any of the epitopes for the antisera examined in Western blot. These results indicate that the beta-subunit of the choriocarcinoma urine hCG has an unusual site which is dissociated into two components of Mr 25,000 (CTP') and Mr 18,000 (FMC) by DTT reduction.

Superoxide generation by alveolar macrophages from aged rats: improvement by in vitro treatment with IFN-gamma.

Alveolar macrophages (AM) from aged rats show an impaired oxidative response, but it is unclear whether or not this is due to the inability of these cells to be activated. To elucidate this, we investigated the capacity of AM from young (16-week-old) and aged (100-week-old) rats to become primed with recombinant rat interferon-gamma (IFN-gamma) for increased phorbol myristate acetate (PMA)-elicited O2- production, utilizing an MCLA-dependent chemiluminescent assay. We also compared concanavalin A- or Bacillus Calmette Guerin (BCG)-induced IFN-gamma production by the spleen cells of young and aged animals. The data indicated that AM freshly harvested from non-sensitized aged rats produced less O2- than those from young animals. A similar result was obtained in BCG-sensitized rats. However, AM from aged rats were primed with in vitro treatment with IFN-gamma for increased rate of O2- production to an equivalent level of that by AM from young animals. In addition, the ability of spleen cells to produce IFN-gamma was well maintained in aged rats. These results suggest that AM function is suppressed in the lungs of aged animals. Our observation that the decreased AM function in aged rats can be reversed is important because it suggests that appropriate treatment may reduce the incidence and mortality of respiratory infections in the elderly.

Huntington's disease gene product, huntingtin, associates with microtubules in vitro.

The gene responsible for Huntington's disease produces a large protein with a molecular weight of approximately 350 k, designated huntingtin. Here, we report that the protein can associate in vitro with the microtubules. Through the process of assembly and disassembly of microtubules, both wild-type and mutant huntingtin associate with microtubules to almost the same degree. Huntingtin does not bind to the tubulin-affinity column directly. Huntingtin appears to interact with polymerized tubulin. These results suggest that huntingtin may have a role in intracellular organelle transport or axonal transport by its association with microtubules.

Cerebral metabolic response to submaximal exercise.

We studied cerebral oxygenation and metabolism during submaximal cycling in 12 subjects. At two work rates, middle cerebral artery blood velocity increased from 62 +/- 3 to 63 +/- 3 and 70 +/- 5 cm/s as did cerebral oxygenation determined by near-infrared spectroscopy. Oxyhemoglobin increased by 10 +/- 3 and 25 +/- 3 micromol/l (P < 0. 01), and there was no significant change in brain norepinephrine spillover. The arterial-to-internal-jugular-venous (a-v) difference for O(2) decreased at low-intensity exercise (from 3.1 +/- 0.1 to 2. 9 +/- 0.1 mmol/l; P < 0.05) and recovered at moderate exercise (to 3. 3 +/- 0.1 mmol/l). The profile for glucose was similar: its a-v difference tended to decrease at low-intensity exercise (from 0.55 +/- 0.05 to 0.50 +/- 0.02 mmol/l) and increased during moderate exercise (to 0.64 +/- 0.04 mmol/l; P < 0.05). Thus the molar ratio (a-v difference, O(2) to glucose) did not change significantly. However, when the a-v difference for lactate (0.02 +/- 0.03 to 0.18 +/- 0.04 mmol/l) was taken into account, the O(2)-to-carbohydrate ratio decreased (from 6.1 +/- 0.4 to 4.7 +/- 0.3; P < 0.05). The enhanced cerebral oxygenation suggests that, during exercise, cerebral blood flow increases in excess of the O(2) demand. Yet it seems that during exercise not all carbohydrate taken up by the brain is oxidized, as brain lactate metabolism appears to lower the balance of O(2)-to-carbohydrate uptake.

Middle cerebral artery blood velocity during a valsalva maneuver in the standing position.

Occasionally, lifting of a heavy weight leads to dizziness and even to fainting, suggesting that, especially in the standing position, expiratory straining compromises cerebral perfusion. In 10 subjects, the middle cerebral artery mean blood velocity (V(mean)) was evaluated during a Valsalva maneuver (mouth pressure 40 mmHg for 15 s) both in the supine and in the standing position. During standing, cardiac output decreased by 16 +/- 4 (SE) % (P < 0.05), and at the level of the brain mean arterial pressure (MAP) decreased from 89 +/- 2 to 78 +/- 3 mmHg (P < 0.05), as did V(mean) from 73 +/- 4 to 62 +/- 5 cm/s (P < 0.05). In both postures, the Valsalva maneuver increased central venous pressure by approximately 40 mmHg with a nadir in MAP and cardiac output that was most pronounced during standing (MAP: 65 +/- 6 vs. 87 +/- 3 mmHg; cardiac output: 37 +/- 3 vs. 57 +/- 4% of the resting value; P < 0.05). Also, V(mean) was lowest during the standing Valsalva maneuver (39 +/- 5 vs. 47 +/- 4 cm/s; P < 0.05). In healthy individuals, orthostasis induces an approximately 15% reduction in middle cerebral artery V(mean) that is exaggerated by a Valsalva maneuver performed with 40-mmHg mouth pressure to approximately 50% of supine rest.

Antagonism of ceruletide, a cholecystokinin analog, to the neurochemical effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine and MK-801, on regional dopaminergic neurons in the rat brain.

In the present study, we investigated the effects of ceruletide (CL), a cholecystokinin analog, on the neurochemical response to non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, phencyclidine (PCP) and MK-801, of the dopaminergic neuron systems in the discrete regions of the rat brain. Systemically administered PCP (7.5 mg/kg, i.p.) or MK-801 (1.0 mg/kg, i.p.) produced significant increases in the tissue contents of dopamine metabolite, homovanillic acid (HVA), in the prefrontal cortex, the nucleus accumbens and the olfactory tubercle but not in the nucleus caudatus putamen after 60 min. The effects of NMDA receptor antagonists in the nucleus accumbens and the prefrontal cortex were partially antagonized by pretreatment with CL (80 and 400 micrograms/kg, i.p., at 60 min prior to the drugs). While CL alone decreased the dopaminergic metabolism only in the nigrostriatal pathways in naive rats, the present results indicated that CL also attenuates the activities of the meso-limbic and meso-cortical dopaminergic neuron systems when these are enhanced by either PCP or MK-801.

The role of endothelin and nitric oxide in modulation of normal and spastic cerebral vascular tone in the dog.

To investigate the roles of endothelin and nitric oxide (NO) in the regulation of cerebral vascular tone under basal conditions and in cerebral vasospasm following subarachnoid hemorrhage in dogs, we used BQ-123 (cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu-) sodium salt), an endothelin ETA receptor antagonist, L-arginine, a substrate for the formation of NO, and NG-nitro-L-arginine methyl ester, an NO synthesis inhibitor, and measured the angiographic diameter of the basilar artery in vivo. In normal dogs, intracisternal (i.c.) injection of BQ-123 (0.6 mg/kg) produced a 29.4 +/- 6.11% (P < 0.01) increase in the basal diameter 24 h after injection. NG-nitro-L-arginine methyl ester (0.6 mg/kg i.c.) produced a 19.3 +/- 2.93% (P < 0.05) decrease in the basal diameter 2 h after injection. This decrease was significantly attenuated by both BQ-123 (0.06-0.6 mg/kg i.c.) and L-arginine (6 mg/kg i.c.), but not by D-arginine. In the two-hemorrhage canine model, BQ-123 significantly inhibited the development of cerebral vasospasm (36.9 +/- 4.11% decrease on day 5 and 42.0 +/- 4.54% decrease on day 6 in controls vs 21.7 +/- 4.75% decrease (P < 0.05) on day 5 and 20.8 +/- 4.14% decrease (P < 0.05) on day 6 for 0.6 mg/kg i.c.) significantly attenuated the cerebral vasospasm on day 4 from a mg/kg i.c.). Furthermore, in this model, L-arginine (6 30.9 +/- 5.78% decrease (before)) to a 12.6 +/- 5.99% decrease (after). The immunoreactive endothelin-1 levels in the endothelial layer and the adventitia of the basilar artery were much higher on days 3 and 7 after the injection of autologous blood than on day 0 before blood injection. These results suggest that endogenous endothelin and NO both participate in regulating the basal tone of cerebral arteries, and, therefore, the development of cerebral vasospasm following subarachnoid hemorrhage may be at least partially attributed to an impairment of the balanced action of endothelin and NO. Furthermore, endothelin ETA antagonists or NO products may be useful in the treatment of cerebral vasospasm following subarachnoid hemorrhage.

A new technique for percutaneous study of lumboperitoneal shunt patency. Technical note.

A new technique for percutaneous imaging of a one-piece lumboperitoneal shunt is described. Patency of the shunt can be assessed by the intraperitoneal spread of contrast medium which is injected intrathecally via the lumbar route. No special equipment or instrumentation is required other than a typical lumbar puncture tray and a general examination tilt table for fluoroscopy.