Atypical retinal microvasculopathy after bone marrow transplantation

Objective : Typical early ischaemic retinal microvascular changes with cotton wool spots after allogeneic bone marrow transplantation (BMT) are well recognised. In this study an atypical non‐ischaemic late retinopathy is described. Methods : Sequential cases of late retinal microvasculopathy following allogeneic BMT were reviewed. Demographic features and clinical and angiographic data were collected. Results : Of 399 patients undergoing allogeneic BMT between 1992 and 1999, eight eyes of four patients developed atypical retinopathy. All patients were male and the age range was 27–50 (mean 37.5) years. The indications for BMT were acute lymphoblastic leukaemia (two patients), chronic myeloid leukaemia (one patient) and chronic lymphocytic leukaemia (one patient). Two patients had conditioning regimens including irradiation. All had cyclosporine and methotrexate as graft‐versus‐host disease prophylaxis. All but one had cyclophosphamide and busulphan as conditioning treatment. One had interferon. No patients had sustained hypertension or diabetes mellitus. Atypical retinopathy was identified 13–62 (mean 50) months after BMT and clinical features consisted of microaneurysms (MA; 4/4), hard exudates (1/4) and macular oedema (1/4). No patient had cotton wool spots. The median acuity was 6/5. Angiographic features were MA (4/4), late leak (2/4) and peripheral (1/4) or central (1/4) ischaemia. One patient underwent focal photocoagulation for macular oedema. Conclusion : Retinal microvascular incompetence (without cotton wool spots) with good vision may occur in a small number of patients as a late complication of allogeneic BMT.     

肺靶向米托蒽醌明胶微球的研究

采用二步法制备米托蒽醌明胶微球,球径范围为5.1～25.0μm的占总数87.36%,体外释药与原药相比t1/2延长4倍,DTA曲线上的特征吸热峰为133℃,经37℃,RH75%考察3月,几乎无变化。经小鼠体内分布试验表明具有明显的肺靶向性,靶向效率增加3～35倍,肺中药代动力学行为可用一室开放模型描述,平均滞留时间延长10h。     

Regulation of responsiveness at D2 dopamine receptors by receptor desensitization and adenylyl cyclase sensitization.

The regulation of cellular responsiveness to dopamine via the D2 dopamine receptor was investigated in mouse fibroblast Ltk-cells stably expressing the rat D2-short receptor [Nature (Lond.) 336:783-787 (1988)]. Dopamine inhibited forskolin-stimulated cAMP levels in these cells (half-maximal inhibition at 3.9 +/- 1.1 nM), and the inhibition by dopamine was blocked by D2 antagonists and was pertussis toxin sensitive. Treatment of these cells with the D2 agonist quinpirole (1 microM) resulted in desensitization of dopaminergic inhibition of forskolin-stimulated cAMP accumulation, with a approximately 4-fold decrease in the potency of dopamine after 1 hr of treatment. No significant changes in total cellular D2 receptor concentrations were observed, even after prolonged agonist treatment. At longer time points, basal and forskolin-stimulated cellular cAMP levels were increased in treated cells. The effect of D2 agonist treatment on membrane adenylyl cyclase (EC 4.6.1.1) activity was examined. Basal and forskolin- and prostaglandin E1-stimulated adenylyl cyclase activities were increased by quinpirole treatment for 24 hr. This sensitization of adenylyl cyclase was blocked by the presence of a D2 antagonist. Pertussis toxin pretreatment blocked the sensitization of adenylyl cyclase by quinpirole, although pertussis toxin also caused increased adenylyl cyclase activity on its own. Sensitization was not dependent upon dopaminergic inhibition of intracellular cAMP levels, because quinpirole treatment in the presence of membrane-permeable cAMP analogs or 3-isobutyl-1-methylxanthine (an inhibitor of cAMP phosphodiesterase) resulted in greater sensitization of adenylyl cyclase activity than quinpirole treatment alone. These results suggest that, in this model system, responsiveness to dopamine via the D2 receptor is regulated by both desensitization of receptor function and sensitization of the stimulatory adenylyl cyclase pathway.     

抗胆碱药3-(2-苯基-2-环戊基-2-羟基-乙氧基)奎宁环烷的立体化学和构效关系

研究了强效抗胆碱药dl-3-(2-苯基-2-环戊基-2-羟基-乙氧基)-奎宁环烷的四个光学异构体的两种不对称合成方法,用HPLC检测了异构体含量,讨论了构效关系。     

Painful bladder disease: clinical and pathoanatomical differences in 115 patients

The diagnostic criteria for interstitial cystitis considered as a subgroup of painful bladder disease (that is sensory bladder disease and chronic abacterial cystitis) are not well established. Some urologists rely on symptoms, while others rely on cystoscopic appearance or pathological findings. Among 115 patients with painful bladder disease we compared symptoms, and cystoscopic and urodynamic findings in those with and without detrusor mastocytosis (28 or more mast cells per mm.2) and attempted to elucidate possible differences between the groups. We chose the pathological anatomical criterion of detrusor mastocytosis to be diagnostic for interstitial cystitis. A total of 43 patients had detrusor mastocytosis and other pathological anatomical signs of interstitial cystitis, and 72 had no mastocytosis but the pathological diagnoses of chronic unspecific cystitis, fibrosis of the bladder, detrusor myopathy, intestinal metaplasia and normal findings. When the 2 groups of patients were compared we found no differences in regard to symptoms (pain, dysuria, frequency, nocturia and urgency), frequency of allergy and hysterectomy, duration of symptoms, petechial bleeding during cystoscopy with bladder distension and cystometric findings. The patients with mastocytosis differed from those without mastocytosis in that they were older, and had a higher frequency of hematuria, a higher frequency of a red, scarred and richly vascularized bladder at cystoscopy before distension, and a smaller cystoscopic bladder capacity. We conclude that by dividing patients with painful bladder into 2 groups according to the mast cell counts in the detrusor, certain differences in the clinical findings in the groups can be ruled out. However, in individual patients one cannot note with certainty to which pathological anatomical group the patient belongs, since great overlapping between the groups exists. Whether only patients with detrusor mastocytosis have interstitial cystitis depends on definitions and still remains an open question.     

Effects of disopyramide on left ventricular function: Assessment by radionuclide cineangiography

To determine the effects of disopyramide on resting systolic left ventricular (LV) function and LV functional reserve, gated equilibrium radionuclide cineangiography was performed at rest and during maximal symptom-limited supine bicycle exercise in 12 patients after a single 300 mg oral loading dose of disopyramide, and in 22 patients (including the 12 patients just mentioned) after they received disopyramide 150 mg 4 times daily for 5 to 10 days (average 7). The oral loading dose (average serum level 3.6 ± 1.3 μg/ml [standard deviation]) produced decreases in ejection fraction in 9 of 12 patients with a decrease in average resting ejection fraction from 40 ± 15% to 33 ± 11% (p <0.005). However, the lower, sustained dosage of disopyramide was associated with a lower average serum level of 2.5 ± 0.8 μg/ml and with smaller but significant decreases in ejection fraction in 3 of 22 patients during exercise only. At this dosage there was no significant decrease in average ejection fraction for the group at rest or during exercise. Adverse effects of disopyramide on ejection fraction occurred even in patients with previously normal LV function at rest. Hence, disopyramide may be associated with significant decreases in LV systolic function, particularly when given in high, oral “loading” doses. However, sustained therapy with lower dosages as well as lower drug levels is also associated with less depression of LV function.     

Positive Cognitive Effects of Bilingualism and Multilingualism on Cerebral Function: a Review

A review of the current literature regarding bilingualism demonstrates that bilingualism is linked to higher levels of controlled attention and inhibition in executive control and can protect against the decline of executive control in aging by contributing to cognitive reserve. Bilinguals may also have smaller vocabulary size and slower lexical retrieval for each language. The joint activation theory is proposed to explain these results. Older trilingual adults experience more protection against cognitive decline and children and young adults showed similar cognitive advantages to bilinguals in inhibitory control. Second language learners do not yet show cognitive changes associated with multilingualism. The Specificity Principle states that the acquisition of multiple languages is moderated by multiple factors and varies between experiences. Bilingualism and multilingualism are both associated with immigration but different types of multilingualism can develop depending on the situation. Cultural cues and language similarity also play a role in language switching and multiple language acquisition.     

Testing a somatization hypothesis to explain the Black–White depression paradox

Social Psychiatry and Psychiatric Epidemiology - Epidemiologic studies document a lower prevalence of major depression in Blacks than Whites in the United States. This is paradoxical from the...