Syndrome of anosmia with hypogonadotropic hypogonadism (kallmann syndrome): Clinical and laboratory studies in 23 cases

We have studied 23 patients (14 men, nine women) in 18 kindreds with anosmia and hypogonadotropic hypogonadism. Seven kindreds had more than one affected member, and included five eugonadal persons with anosmia and two eusomic women with hypogonadotropic hypogonadism. Other clinical abnormalities observed included: obesity (in nine), cryptorchidism (six), osteopenia (six), mild neurosensory hearing loss (five), gynecomastia (five), diabetes mellitus (four), cleft lip or palate or both (three), high-arched palate (two), short fourth metacarpal (two), and clinodactyly, camptodactyly, shortened frenulum of the tongue, multiple facial anomalies, right-sided aortic arch, malrotation of the gut, renal diverticulum, and mild red-green color blindness (one each).Normal secondary sex characteristics developed in all 20 patients treated on a long-term basis with chorionic gonadotropin or gonadal steroids. Responses to a single injection of gonadotropin-releasing hormone were heterogeneous. Five men had no luteinizing hormone response, five had a depressed response, and one an exaggerated response; two had no follicle-stimulating hormone response, five responses were depressed, three were normal, and one was ex-aggerated. None of seven women achieved a normal luteinizing hormone response to gonadotropin-releasing hormone; two had depressed follicle-stimulating hormone response, four responses were normal, and one was exaggerated. None of 11 patients tested responded to clomiphene. Two men fathered children. Each of two other men who underwent biopsy of the testes before and after long-term chorionic gonadotropin therapy showed mildly increased spermatogenesis. Little or no maturation beyond primordial follicles was observed in two ovarian biopsy specimens. Fifteen of 17 patients had normal basal prolactin levels and 14 of 16 had normal thyrotropin-releasing hormone-induced prolactin increase, but nine of 15 tested had a decreased or absent response of prolactin to chlorpromazine. Circulating concentrations of thyroid hormones were normal, but four of 17 patients tested had depressed TSH (thyroid-stimulating hormone) responses to thyrotropin-releasing hormone, and one man had an exaggerated response. Three of 12 patients had a depressed cortisol response to insulin-induced hypoglycemia, and two of seven patients had slightly depressed deoxycortisol responses to metyrapone. Growth hormone and vasopressin release in all 14 and all 12 patients, respectively, studied were essentially normal.Patients with anosmia and hypogonadotropic hypogonadism may have hypothalamic defect(s) responsible for the hypogonadotropism and perhaps for certain additional deficiencies of anterior pituitary function found in some. The cause of less frequent phenotypic abnormalities has not been established. In certain pedigrees, the evidence suggests that the major manifestations of the syndrome are inherited as an autosomal recessive trait.     

Relationship between somatostatin and interleukin-6: A cross-sectional study in patients with acute pancreatitis

Objectives

The aim of the analysis is to determine dynamic changes in somatostatin (SS) and interleukin-6 (IL-6) concentrations during in acute pancreatitis (AP).

p11 modulates L-DOPA therapeutic effects and dyskinesia via distinct cell types in experimental Parkinsonism

The reduced movement repertoire of Parkinson’s disease (PD) is mainly due to degeneration of nigrostriatal dopamine neurons. Restoration of dopamine transmission by levodopa (L-DOPA) relieves motor symptoms of PD but often causes disabling dyskinesias. Subchronic L-DOPA increases levels of adaptor protein p11 (S100A10) in dopaminoceptive neurons of the striatum. Using experimental mouse models of Parkinsonism, we report here that global p11 knockout (KO) mice develop fewer jaw tremors in response to tacrine. Following L-DOPA, global p11KO mice show reduced therapeutic responses on rotational motor sensitization, but also develop less dyskinetic side effects. Studies using conditional p11KO mice reveal that distinct cell populations mediate these therapeutic and side effects. Selective deletion of p11 in cholinergic acetyltransferase (ChAT) neurons reduces tacrine-induced tremor. Mice lacking p11 in dopamine D2R-containing neurons have a reduced response to L-DOPA on the therapeutic parameters, but develop dyskinetic side effects. In contrast, mice lacking p11 in dopamine D1R-containing neurons exhibit tremor and rotational responses toward L-DOPA, but develop less dyskinesia. Moreover, coadministration of rapamycin with L-DOPA counteracts L-DOPA–induced dyskinesias in wild-type mice, but not in mice lacking p11 in D1R-containing neurons. 6-OHDA lesioning causes an increase of evoked striatal glutamate release in wild type, but not in global p11KO mice, indicating that altered glutamate neurotransmission could contribute to the reduced L-DOPA responsivity. These data demonstrate that p11 located in ChAT or D2R-containing neurons is involved in regulating therapeutic actions in experimental PD, whereas p11 in D1R-containing neurons underlies the development of L-DOPA–induced dyskinesias.Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons projecting from substantia nigra pars compacta (SNc) to striatum, eventually resulting in bradykinesia, rigidity, resting tremor, and postural imbalance (1). Dopamine replacement strategies are effective for many motor symptoms. At early stages, MAO-B inhibitors or dopamine D2 receptor agonists may provide sufficient symptomatic relief, but as the disease progresses essentially all patients will require treatment with levodopa (L-DOPA) (1). Following decarboxylation, L-DOPA is converted to dopamine acting on both dopamine D1 and D2 receptors. D1 and D2 receptors are segregated in striatonigral and striatopallidal pathway neurons, respectively (2). Activation of D1 and D2 receptors causes synergistic stimulation of locomotion, explaining the stronger anti-Parkinsonian action of L-DOPA compared with selective D2 receptor agonists (1, 2). Whereas dopaminergic agents often successfully treat bradykinesia and rigidity in PD, additional therapy with anticholinergic agents is sometimes required for optimal treatment of resting tremor (1). Moreover, the therapeutic effect of L-DOPA is gradually shortened as disabling dyskinetic side effects emerge (3). There is no licensed treatment against L-DOPA–induced dyskinesias (LIDs).Targeting the serotonergic, glutamatergic, and/or cholinergic systems have been reported to counteract LIDs (3). p11 (i.e., S100A10) is a member of the S100 EF-hand protein family, which increase the levels of distinct serotonin (5-HT_1BR and 5-HT₄R) and glutamate (mGluR5) receptors at the cell surface, resulting in enhanced effects on cell signaling via these receptors (4, 5). p11 is widely expressed in the brain with particularly high levels in cholinergic neurons (6–9). p11 is regulated by a variety of stimuli and therapies, most notably antidepressants (4). p11 is strongly up-regulated in the striatum following repeated treatment with L-DOPA in the 6-OHDA–lesioning model of experimental parkinsonism (10). p11 can therefore influence several pathways implicated in LIDs.In the present study, we examined global and cell-specific conditional p11 knockout (KO) mice in experimental Parkinsonism models to identify the brain circuitries that mediate p11-dependent therapeutic effects of L-DOPA as well as LIDs.     

Effects of calcium channel blocking agents on reperfusion arrhythmias

The effect of the calcium antagonists nifedipine (NF) and diltiazem (DT) on reperfusion after release of circumflex coronary artery (CX) occlusion was studied in open-chest dogs. Dogs were randomized to receive a bolus of 5 μg/kg NF (seven dogs), 1 μg/kg NF (nine dogs), or vehicle (nine dogs). After bolus, high and low dose NF dogs were infused with 1 μg/kg/min NF. All dogs then underwent 30 minutes CX occlusion followed by reperfusion. Dogs that did not develop ventricular fibrillation (VF) in the first 10 minutes of reperfusion were considered survivors. NF caused a dose-related increase in CX blood flow and decrease in mean arterial pressure (MAP), significant at the higher dose. Reperfusion VF occurred in five of nine low dose NF dogs, five of seven high dose NF dogs, and five of nine controls. Another 21 dogs were randomized to receive a bolus of 0.2 mg/kg DT (11 dogs) or vehicle (10 dogs). Infusion rates (and an additional bolus injection, if necessary) were chosen to produce a 10 to 20 mm Hg drop in MAP. CX occlusion and reperfusion were performed as above. Reperfusion VF occurred in 9 of 11 DT dogs vs 8 of 10 controls. Thus neither nifedipine nor diltiazem enhanced survival during reperfusion of myocardium previously subjected to 30 minutes of ischemia.     

Comparison of late (62 to 140 months) degenerative changes in simultaneously implanted and explanted mitral valve positions in six patients

A Hancock porcine bioprosthesis (PB) was simultaneously implanted in each of 6 patients aged 30 to 64 years (mean 45) in the tricuspid and mitral valve positions and both PBs were explanted 62 to 140 months (mean 102) later. Cuspal degenerative changes occurred in all 12 PBs. In 5 patients, the changes were more extensive on the PBs in the mitral position than in those in the tricuspid position. Cuspal calcific deposits, as determined by radiographs of the explanted bioprostheses, occurred in 5 PBs in the mitral position and in 3 in the tricuspid position: 1 patient with calcific deposits in the PB in the mitral position had no calcific deposits in the corresponding PB in the tricuspid position; 1 patient had heavy calcific deposits in the PB in the mitral position and only mild deposits in the PB in the tricuspid position; and 3 patients had similar but mild calcific deposits in both PBs. Cuspal tears occurred in 5 of the 6 PBs in the mitral position and in no PB in the tricuspid position. Thrombus was observed on the ventricular aspects of the bioprosthetic cusps in 1 PB in the mitral position and in 4 PBs in the tricuspid position. Thus, in our 6 patients, the degenerative changes were more extensive in the PBs in the mitral position than in those in the tricuspid position. These observations indicate that wear characteristics of simultaneously implanted PBs vary according to the site of implantation.     

慢性阻塞性肺疾病患者血浆白介素17水平变化及其与白介素8、白三烯B4相关性的研究

目的观察慢性阻塞性肺疾病（COPD）急性加重期患者和急性加重期缓解患者的血浆白介素17（IL-17）、白介索8（IL-8）及白三烯B4（LTB4）含量变化。同时观察COPD患者血浆IL-17与IL8及LTB4含量的相关性。方法随机抽取COPD急性加重期患者、急性加重期缓解患者各35例，健康对照者15例，采用双抗夹心ELISA法测定三组人群血浆IL-17、IL-8、LTB4含量。结果COPD急性加重期患者血浆IL-17、IL-8及LTB4水平明显高于急性加重期缓解患者和健康对照者，差异有统计学意义（P〈0．05），COPD急性加重期缓解患者血浆IL-17、IL-8及LTB4水平亦明显高于健康对照者，差异有统计学意义（P〈0．05）。COPD急性加重期患者和急性加重期缓解患者血浆ID8、LTB4含量均与IL-17呈正相关。结论IL-17参与了COPD的炎症过程，而与IL-8、LTB4呈正相关。