Stroke: prevention and estimation of risks.
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Biomedical subjects
Publications and source records attributed to F Negri.
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The posterior sagittal anorectoplasty (PSARP) is widely recognized as the best technique available today for the surgical treatment of anorectal malformations (ARM). However, different retrospective studies on the functional results of PSARP in the treatment of ARM have shown different postoperative degrees of constipation. In particular, even in patients with normal sacrum, about 70% of operated ARM with vestibular fistula and about 50% with perineal fistula can be complicated by fecal constipation and pseudoincontinence. In order to identify preoperatively whether ARM patients present abnormal innervation patterns of rectal pouch and fistula (as reported by Holschneider et al [7]), we decided to study suction rectal biopsies performed by introducing SBT-100 rectal suction biopsy tool into the fistula at 6, 4, 3 and 2 cm from the meatus. To date, this approach has been adopted in 22 ARM cases (15 females and 7 males, age range 7 days-4 years), 6 of them with recto-vestibular fistula and 13 with recto-perineal fistula. Biopsies were frozen in isopentane at liquid nitrogen temperature and cryostatic sections were studied by acetylcholinesterase (AChE), succinic-dehydrogenase (SDH) and alpha-naphthyl-esterase (ANE) enzymo-histochemical techniques. The results concerning the innervation-type of fistula and proximal rectal pouch were confirmed by the biopsies obtained during PSARP. Our overall incidence of rectal innervation intrinsic disorders was 81.82%. In particular, all our cases of vestibular fistula presented associated dysganglionoses. The incidence of associated Hirschsprung's disease was high, corresponding to 18% of cases. Our results suggest that the high frequency of constipation in low forms of ARMS depends on primary intestinal neuronal malformations and it cannot be ascribed to a denervation secondary to rectal dissection and to PSARP procedure. We propose the introduction of this type of preoperative enzymo-histochemical diagnosis in ARM cases because it can select those patients with severe associated dysganglionoses. In our opinion, if this diagnosis is available preoperatively, PSARP can be performed without using abnormally innervated structures and reducing postoperative functional complications.
BACKGROUND/PURPOSE: In 1996, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET transmembrane receptor. In the same year, GDNF mutations were found in association with RET protooncogene mutations in Hirschsprung patients. Mutations in GDNF per se are thought neither necessary nor sufficient to cause Hirschsprung's disease (HD). To date, our study group has identified GDNF mutations only in 2 of 98 cases of intestinal dysganglionosis. The aim of our study was to investigate a possible expression deficit of GDNF in the enteric nervous system of Hirschsprung patients not mutated for the GDNF gene. METHODS: We used rabbit polyclonal antibodies raised against a peptide corresponding to amino acids 186-205 mapping within the carboxy-terminal domain of human GDNF. GDNF expression was studied immunohistochemically in surgical specimens from 30 HD cases (27 classic forms and 3 ultralong forms) and from 10 age-matched controls. Serial sections from the same full-thickness specimens were investigated with the following histochemical and immunohistochemical techniques: acetylcholinesterase, lactate dehydrogenase, succinic dehydrogenase, alpha-naphthyl-esterase, glial fibrillary acid protein, S-100 protein, and neuron-specific enolase. RESULTS: A high level of GDNF expression was found in normal intestine and in Hirschsprung ganglionic segment. Satellite elements of myenteric ganglia presented a strong immunoreactivity to GDNF. Conversely, the aganglionic segment showed cholinergic hyperinnervation and hypertrophic trunks of nerve fibers in the muscular interstitium with complete absence of GDNF expression. The small ganglia of the hypoganglionic segment showed a reduced GDNF immunoreactivity. CONCLUSIONS: GDNF, a distantly related member of the transforming growth factor-beta superfamily, is a potent neurotrophic and survival factor for neurons and enteric ganglion cells. Mutations of the GDNF gene or GDNF expression deficit interrupt the faithful GDNF signaling via Ret, contributing to HD pathogenesis.
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We describe a child with Wilms' tumor (WT) which occurred in an unequivocal multicystic dysplastic kidney (MDK). We indicate a current nonsurgical approach to MDK, but stress the probable malignant degeneration of blastemal cells, the need to search carefully for the WT in the MDK, and the necessity on 3-monthly follow-up US studies.
The authors report on a newborn admitted to the Intensive Care Unit of Gaslini Institute for serious respiratory insufficiency who died on the third day of life because of a sepsis due to Listeria monocytogenes. The authors focus on the patient's history and clinical picture and on the histological evaluation of the lesions observed. The importance of infection in pregnancy and the possible severe consequences of listeriosis on the foetus are underlined, stressing the need for early diagnosis and adequate treatment.
In the present investigation insulin-induced hypoglycemia was used as a powerful stimulus to rapidly release epinephrine from the adrenal medulla. Insulin injection raised epinephrine 16-fold and doubled norepinephrine plasma levels. The aim of this attempt was to induce beta-adrenergic receptors (beta-ARs) sequestration in vivo on mononuclear leukocytes (MNLs). The number of total and surface beta-ARs was significantly increased 30 minutes after insulin administration, with only partial recovery at 90 minutes. No detectable receptor sequestration was observed: surface receptors were about 90% of total receptors in all the conditions examined. Isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) accumulation was also increased after 30 minutes (+66%) and 90 minutes (+65%) of insulin injection. Basal and forskolin-stimulated intracellular cAMP values were unchanged. We conclude that, even after a strong release of catecholamines, beta-AR redistribution cannot be demonstrated on MNLs.
Indenolol is a new antihypertensive agent, whose beta 1-adrenoceptor antagonist properties combined with beta 2-adrenoceptor agonist properties have been shown by experimental studies in animals. Our previous work reported that in vivo beta-adrenoceptor blocking drugs markedly increase the beta-adrenoceptor (BAR) number, without increasing BAR affinity. The aim of this study was to evaluate BAR density and affinity before and after indenolol therapy in membranes of polymorphonucleates (PMN) of patients with essential hypertension. Polymorphonuclear binding parameters were studied in 12 hypertensives (WHO stages I and II) after 14 days of placebo and after 21 days of indenolol therapy (120 mg once daily orally). Indenolol did not increase BAR number but significantly decreased (P less than 0.01) BAR affinity. On the basis of these data it is concluded that indenolol does not induce the same changes in PMN's BAR as previously observed with oxprenolol, propranolol and labetalol. This phenomenon may account for the absence of rebound effect after withdrawal of indenolol in hypertensives.
Indenolol hydrochloride is a recently introduced antihypertensive substance. Although it has beta-adrenoceptor blocking activity, its action is due to total peripheral resistance reduction. We investigated the effects of indenolol therapy on left ventricular performance in 15 patients with essential hypertension. Assessments were made using systolic time intervals and computerized echocardiography. The echocardiographic and mechanocardiographic tracings were recorded three times: at the beginning of the trial, after seven days of placebo, and after three weeks of indenolol treatment. The indenolol therapy significantly decreased (P less than 0.001) systolic and diastolic blood pressures and heart rate in all patients, both in supine and standing positions. After three weeks of treatment, systolic time intervals and echocardiographic determinants of left ventricular function were substantially unchanged in comparison with the basal and placebo evaluations. We conclude that indenolol exerted a marked effect on chronotropism but no demonstrable negative effect on inotropism in patients with essential hypertension. No clinical signs of heart failure were recorded. Side effects were absent, and patient compliance was good in all cases.
Number and affinity of beta-adrenoceptors in human polymorphonucleates (PMN's) have been studied in patients with essential hypertension (n = 12) and in normal subjects of the same range of age and sex (n = 16). (-)Diidroalprenolol-H3 has been utilized as ligand. Membranes preparation was performed according to Galant (5). Number of beta-adrenoceptor is significantly decreased compared with controls (p less than 0.05), both with saturation curves and Scatchard analysis. Affinity of beta-adrenoceptors toward (-)diidroalprenolol-H3 is lightly increased but not significantly. These data could be explained on the basis of the desensitization occurring in hypertensive subjects by altered plasma catecholamines level, as in experimental in vitro systems.
A logistic model was used to analyze the pattern of affected relatives of probands with primary affective disorders (PAD). The sample consisted of 242 patients, diagnosed as either unipolar (UP, 107) or bipolar (BP, 135) and 430 control nonpsychiatric inpatients and all first degree relatives of both groups. Age correction was applied to both groups. The analysis showed a significant baseline increase in frequency of PAD among relatives of PAD probands with siblings more likely to be affected than parents. The difference in frequency of PAD according to sex of relative almost reached significance. Specific diagnosis (UP or BP) of proband did not significantly affect the probability of relatives becoming ill. Genetic models incorporating sex-specific thresholds were able to explain the data satisfactorily as resulting from either Single-Major-Locus inheritance or Multifactorial-Polygenic inheritance.
Psychiatric disorders in a sample of spouses of probands with recurrent Primary Affective Disorders (PAD) and in their first degree relatives were evaluated and compared with those in the spouse of control subjects without psychiatric illnesses. No differences were found in the risk for PAD, but spouses of PAD patients and their respective first degree relatives manifested a greater incidence of affective spectrum disorders.
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The interference of chlorpromazine (CPZ) and several preincubated CPZ metabolites on the lymphocyte absorption of antibodies directed against HLA-A1 and other nonrelated HLA specificities were investigated. Both CPZ and metabolites 7-OH-, Nor1-, and Nor2-CPZ were found to interfere with the specific absorption of anti-HLA-A1 antibodies. The meaning of such a result is discussed.
Seventy-two spouses of subjects with recurrent primary affective disorders (PAD), were investigated for the presence of psychiatric disorders in their lives and in those of their first degree relatives, and compared with 71 spouses of non-psychiatrically ill control subjects. No difference was found in the risk for PAD; on the other hand spouses of affective patients manifested a greater occurrence of psychiatric disorders belonging to the affective spectrum, as did their respective first-degree relatives.
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Pretherapeutic urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was studied in 25 primary depressed patients. The results indicate that: (i) There exists a wide variability among primary depressives with respect to MHPG excretion. (ii) Age of onset together with polarity of the disease may account for the nonhomogeneous division of the patients according to MHPG levels. (iii). The other variables considered, with the possible exception of motor activity, do not explain the dichotomy between high or normal and low MHPG levels, even though it is possible that they influence MHPG excretion to some extent, with the consequent possibility of errors in subclassification of the patients at the boundaries between the two groups. (iv) The correlation between motor retardation and low MHPG excretion is positive, but probably due to a frequent association between this motricity state and primary depression of bipolar early onset type. (v) Treatments with chlorimipramine and, to a lesser degree of specificity, with amitriptyline are particularly indicated in patients with normal or high MHPG. Some practical and theoretical implications deriving from these data are briefly discussed.
Abnormal anterior pituitary (AP) responsiveness to acute administration of thyrotropin-releasing hormone (TRH) and luteinizing hormone-follicle stimulating hormone-releasing hormone (LH-RH) was investigated in 14 patients (two men and 12 women) suffering from primary affective disorders. In ten, TRH, 500 microgram given intravenously, induced a rise in plasma growth hormone (GH) level, while in eight patients it induced a rise in plasma levels of FSH or LH or both. When LH-RH, 150 microgram was administered intravenously to ten patients, it induced a rise in plasma GH level in one patient and increased plasma prolactin level in three patients. Collectively, in only three of 14 patients was conventional AP responsiveness to hypothalamic neurohormones present. These findings demonstrate the existence of a profound derangement of AP responsiveness to hypothalamic neurohormones in depressed patients and suggest that a primary alteration in the physiologic links between the central nervous system and the AP may be at the origin of the neuroendocrine disturbance.