Alice in wonderland syndrome "through the looking-glass" in a rare presentation of non-convulsive status epilepticus in cerebral venous sinus thrombosis and COVID-19.

Alice in Wonderland Syndrome (AIWS) is a rare perceptual disorder, rarely associated with epileptic etiology. We report the case of a 23-year-old man with subacute onset of right peri-orbital headache and visual misperceptions consistent with AIWS Type B, who underwent laboratory tests, brain CT with venography, ophthalmic examination, and neurological assessment that turned out to be normal except for visuospatial difficulties and constructional apraxia. A nasopharyngeal SARS-CoV2 swab taken as screening protocol was positive. The EEG performed because of the persistence of AIWS showed a focal right temporo-occipital non-convulsive status epilepticus; a slow resolution of clinical and EEG alterations was achieved with anti-seizure medications. Brain MRI showed right cortical temporo-occipital signal abnormalities consistent with peri-ictal changes and post-contrast T1 revealed a superior sagittal sinus thrombosis, thus anticoagulant therapy was initiated. AIWS is associated with temporo-parieto-occipital carrefour abnormalities, where visual and somatosensory inputs are integrated to generate the representation of body schema. In this patient, AIWS is caused by temporo-occipital status epilepticus without anatomical and electroencephalographic involvement of the parietal region, consistent with the absence of somatosensory symptoms of the syndrome. Status epilepticus can be the presenting symptom of cerebral venous sinus thrombosis (CVST) which, in this case, is possibly due to the hypercoagulable state associated with COVID-19.

[Latex allergy in hospital workers--follow-up of symptomatic subjects]. / L'allergia al lattice tra i dipendenti dell'ospedale di Terni: follow-up dei soggetti sintomatici.

Latex allergy may be manifested in a variety of clinical disturbances such as contact urticaria, angioedema, rhinoconjunctivitis, asthma, and anaphylactic reactions. The aim of this follow-up study was to determine whether a change in glove use from powdered to powder-free latex gloves at previously surveyed hospital workers reduced the work-related symptoms. 53 hospital workers with work-related symptoms where followed up 4,6 years after first investigation. On re-examination, 54.7% use both powdered and powder-free gloves, 37.7% used only latex free gloves and 7.6% stopped the glove use. At follow-up, in 68% of subjects there was the remission or the improvement of work-related symptoms. The improvement of symptoms was greater in workers using powder-free gloves than in others (p < 0.005). In conclusion our study shows that preventive measures, such as the use a powder-free latex gloves, are sufficient to induce a reduction of work-related symptoms.

[Have the prevalence and incidence of occupational asthma and rhinitis due to laboratory animals declined in the last 25 years?]. / La prevalenza e l'incidenza dell'asma e della rinite occupazionale da animali di laboratorio si sono ridotte negli ultimi 25 anni?

Data for time trends in the prevalence of occupational asthma (OA) and rhinitis (OR) are not known. To investigate trends in the prevalence and incidence of OA and OR over time, we reviewed the available literature. We analysed 15 cross-sectional and 4 longitudinal studies published from 1980 to 2006. In workers exposed to laboratory animals (LA) the prevalence of OA ranged from 2.2% to 11.7%; the prevalence of OR ranged from 6.7% to 41.7%. When we analysed prevalence by study date using a logistic model, the estimated prevalence of OA declined from 8.7% in 1976 to 4.2% in 2001 (p < 0.003), which is -1.8% every ten years. The prevalence of OR rose slightly from 18.5% in 1976 to 19.7% in 2001 (NS). In four longitudinal studies the incidence of OA ranged from 0.4 to 3.5/100 person years, while the incidence of OR ranged from 2.0 to 10.1/100 person years. No clear trend emerged over time. This review shows a trend toward a progressive decline in the prevalence of occupational asthma due to laboratory animals, which may be due to the reduction of exposure since the early 1980s. A further reduction of exposure is needed to prevent the onset of occupational rhinitis.

Genetic and hormonal characterization of cryptic 21-hydroxylase deficiency.

Cryptic 21-hydroxylase deficiency has been previously described in asymptomatic family members of patients with classical congenital adrenal hyperplasia (CAH). These family members were detected by high baseline 17-hydroxyprogesterone levels found in the course of family studies. The hormonal responses to ACTH of the family members with cryptic 21-hydroxylase deficiency were determined and compared to the responses of patients with CAH, patients with acquired adrenal hyperplasia, family members predicted to be heterozygous for CAH, family members predicted to be unaffected, and the general population. The ACTH-stimulated levels of 17-hydroxyprogesterone and delta 4-androstenedione in the cryptic family members were elevated above the level of the general population or family members heterozygous for classical CAH, but below that of patients with CAH. The hormonal profile of patients with cryptic 21-hydroxylase deficiency is similar to that of patients with acquired adrenal hyperplasia. The response of family members heterozygous for the cryptic gene (21-OH CRYPTIC/21-OH NORMAL) was indistinguishable from that of family members heterozygous for the classical CAH gene (21-OH CAH/21-OH NORMAL). These studies support our previous proposal that patients with cryptic 21-hydroxylase deficiency are genetic compounds, having one gene for a severe enzyme deficiency and one gene for a mild 21-hydroxylase deficiency. Thus, the 21-hydroxylase genotype in cryptic 21-hydroxylase deficiency is 21-OH CAH/21-OH CRYPTIC.

Cryptic 21-hydroxylase deficiency in families of patients with classical congenital adrenal hyperplasia.

Serum androgens and 17-hydroxyprogesterone concentrations and HLA genotypes were determined in 124 families of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). In 8 pedigrees, we discovered 16 pubertal or postpubertal family members of either sex who had biochemical evidence of 21-hydroxylase deficiency but were without clinical symptoms of excess virilism, amenorrhea, or infertility. We designated these family members as individuals with cryptic 21-hydroxylase deficiency. Within each generation, the family members with cryptic 21-hydroxylase deficiency were HLA identical. It is proposed that these family members are genetic compounds, having 21-hydroxylase deficiency as a result of two recessive gene defects: 1) a severe 21-hydroxylase gene defect present in the index case with classical CAH (21-OHCAH) and 2) a mild 21-hydroxylase gene defect (21-OHCRYPTIC). Thus, the CAH genotype in the family members with cryptic 21-hydroxylase deficiency is 21-OHCAH/21-OHCRYPTIC. Lod score analysis for linkage between the cryptogenic 21-OH trait and HLA gave a combined Lod score for males and females of theta = 0.00 of 3.409. Close genetic linkage between HLA and 21-OHCRYPTIC was thus established. This study provides support for the previously reported heterogeneity of 21-hydroxylase deficiency which may result from allelic variability at the locus for steroid 21-hydroxylase.

Interleukin-1beta (IL-1beta) and IL-6 modulate insulin-like growth factor-binding protein (IGFBP) secretion in colon cancer epithelial (Caco-2) cells.

Chronic inflammation is characterised by modifications in cytokine concentrations, whereas growth is mainly dependent on the GH-IGF axis. IGF-I bioavailability is modulated by a family of IGF-binding proteins (IGFBPs). The aim of the present study was to evaluate the interactions among interleukin-1beta (IL-1beta), IL-6 and IGFBP secretion by intestinal cells to assess whether cytokines modulate IGFBP secretion, and in turn IGF-I and IGF-II bioavailability. The human colon carcinoma derived cell line Caco-2 was used as an in vitro model for its capacity to differentiate spontaneously. Experiments were carried out on day 4 (undifferentiated state) and day 14 (differentiated state) after plating. Carcinoembryonic antigen (CEA) was used as a marker of differentiation and increased in the conditioned media (CM) from days 4 to 14 (0.2+/-0.01 ng/ml per 10(5) cells vs 3.3+/-0.2 ng/ml per 10(5) cells, P<0.05). IGFBP-2 and IGFBP-4 secretion decreased concomitantly. Cells were stimulated with IL-1beta and IL-6 at 1, 10 and 50 ng/ml, and with IL-1beta and IL-6 in combination at the same dose of 1 and 10 ng/ml. IGF-I at 50 ng/ml was used as a control. Caco-2 cells expressed and secreted mainly IGFBP-2 and IGFBP-4 into the CM. On day 4, IL-1beta (1 ng/ml) and IL-6 (10 and 50 ng/ml) reduced IGFBP-2 by 29+/-8%, and by 32+/-9 and 38+/-8% respectively (P<0.05). IGFBP-4 was also reduced by IL-1beta at 1 and 50 ng/ml (-14+/-4% and -46+/-11% vs serum free medium (SFM) respectively, P<0.05), and IL-6 at 50 ng/ml (-46+/-15%, P<0.05). Both IGFBP-2 and IGFBP-4 were reduced by IL-1beta and IL-6 in combination at 1 and 10 ng/ml (P<0.05). On day 14, IGFBP-2 band intensity was reduced at 10 ng/ml of IL-1beta (-22+/-15% vs SFM, P<0.05) and at 50 ng/ml of both cytokines (-33%+/-8% and -13%+/-13% vs baseline respectively, P<0.05). IGFBP-4 band intensity decreased with 10 and 50 ng/ml of IL-1beta (-35+/-11% and -46+/-15% vs SFM respectively) and IL-6 (-36%+/-10% and -46+/-15% vs SFM respectively). IL-1beta and IL-6 in combination at 1 and 10 ng/ml reduced both IGFBP-2 and IGFBP-4.In conclusion, IGFBP-2 and IGFBP-4 secretion in CM decreased with Caco-2 cell differentiation. IGFBP-2 and IGFBP-4 were significantly decreased by IL-1beta and IL-6 treatment in both the undifferentiated and differentiated state. Furthermore, these cytokines increased cell proliferation whereas total protein content was significantly reduced only at the higher concentrations of IL-6 and IL-1beta. These findings suggest that interleukins modulate the IGF-IGFBP system in Caco-2 cells in vitro.

Dynamics of 24-hour pulsatile cortisol, 17-hydroxyprogesterone, and androstenedione release in prepubertal patients with nonclassic 21-hydroxylase deficiency and normal prepubertal children.

To assess whether the quantitative and qualitative aspects of cortisol, 17-hydroxyprogesterone (17-OHP), and androstenedione (D4A) secretion in patients with nonclassic congenital adrenal hyperplasia (NCCAH) differ from those in normal children, 24-hour serum concentrations of these steroids were measured in five prepubertal patients with NCCAH and five normal prepubertal children. Adrenal steroid profiles obtained by 30-minute sampling were analyzed by the Pulsar program. In comparison to normal children, the 24-hour quantitative parameters of 17-OHP and D4A secretion were significantly greater in NCCAH patients, but serum cortisol concentrations were similar in the two groups. When daytime and nighttime hormone releases were separately analyzed, a significant nocturnal elevation of the cortisol area under the curve above zero level (AUCo) and 12-hour mean and 17-OHP AUCo, AUC above baseline, mean peak height, amplitude, area, and 12-hour mean was detected in normal subjects only. Conversely, NCCAH patients exhibited an increased frequency and number of 17-OHP secretory peaks at night together with a reduction of the interpeak interval. No significant day/night differences in D4A concentrations were detected either in normals or in the patients. In conclusion, the results of the present study indicate that patients with NCCAH have a distinct pattern of adrenal steroid secretion characterized by a high-frequency 17-OHP release accompanied by a relative nocturnal cortisol deficiency.

Blood pressure tracking in adolescents with insulin-dependent diabetes mellitus.

Hypertension, one of the most frequent and important complications of insulin-dependent diabetes mellitus (IDDM), usually begins in the second decade of the disease and is rare in childhood. We analysed the blood pressure (BP) levels of 106 patients (48 males, 58 females, aged 2-16 years) in relation to sex and age and we studied the modification of BP with years (tracking). BP levels, registered every three to six months, were compared with the local standard levels for age and expressed as standard deviation scores (SDS) of the means. For each subject a regression line describing the change of the SDS over time was calculated by the method of least squares. The slope of this line is called trend and represents the tendency of BP to increase or decrease with time, i.e. to develop (or not) hypertension. All patients, except one 16 year old girl, had normal BP and no microalbuminuria but ten of them presented with mean levels in the upper quartile and/or a constantly upward BP trend and were considered at risk. After a three year follow-up four of these ten patients became frankly hypertensive with increased microalbuminuria. These results agree with previous findings and with the hypothesis that an increase of intraglomerular and/or systemic BP may precede the appearance of (and even could be responsible for) microalbuminuria. The BP tracking study in IDDM children and adolescents could be useful for an early recognition of patients at risk of developing hypertension and diabetic nephropathy.

Juvenile rheumatoid arthritis in Turner's syndrome.

An increased risk for autoimmune diseases has been recognized in Turner's syndrome (T.S.). However autoimmune rheumatic or connective tissue disorders have not been described. We report here on a 8-8/12 year old caucasian girl with T.S. and Juvenile Rheumatoid Arthritis (JRA). The hypothesis that the association is more than casual is discussed.

[The association between hypothyroidism and other congenital defects. The experience of the National Registry in 1987-1992]. / Associazione tra ipotiroidismo e altri difetti congeniti. L'esperienza del Registro Nazionale negli anni 1987-1992.

This study considers the birth defects (BD) observed from 1987 to 1992 in 35/811 newborns with congenital hypothyroidism (CH) diagnosed by neonatal screening and included in the National Register. The BD incidence was higher than in the general population (4.3 vs 2.5-3%) and especially the one of the congenital heart diseases, (CHD) (2.1 vs 0.3-0.8%). Furthermore the CHD were more frequently observed in females than in males (M/F = 1/4.7). These results seem not to be casual but the reasons remain unknown. The most frequent CHD observed were the septal defects and the pulmonary stenosis. Further are presented and discussed the main findings of 2 groups of CH patients (with and without BD). These results are a good instance of the National Register applications, also for less known aspects of the CH like the concomitant BD.

[National Register of congenital hypothyroidism]. / Il registro nazionale degli ipotiroidei congeniti.

The results of five years activity of the National Register of children with Congenital Hypothyroidism (NRCH) have been evaluated. NRCH was established in Italy in 1987, as a pilot project of Health Ministry. All Italian Centers in charge of the screening, treatment and follow-up of CH are involved in the program. The results have provided further epidemiological informations about CH in Italy and have evidenced some aspects in the screening organization which had to be improved. Discussion of Register data in annual meetings has recently allowed to obtain an improvement especially for the beginning of treatment and the used dose of therapy.

[Neonatal screening in congenital hypothyroidism in Italy. The National Registry]. / Lo screening neonatale dell'ipotiroidismo congenito in Italia. Il Registro Nazionale.

Neonatal screening for congenital hypothyroidism (CH) began in Italy in 1977 and then progressively developed covering 97% of live births in 1992. The National Register of infants with congenital hypothyroidism was established in 1987 as a project of the Health Ministry and is coordinated by the Italian Institute of Health. The aim of the Register is to provide disease surveillance, to monitor the efficiency and effectiveness of neonatal screening and to allow the identification of possible etiological risk factors in congenital hypothyroidism. The results of the Register provided valuable epidemiological informations about congenital hypothyroidism in Italy and evidenced several areas in whom an increased incidence probably caused by iodine deficiency was observed. Discussion of Register data during annual national meetings has allowed an improvement of the screening program with particular regard to the beginning of therapy with L-thyroxine and its dose. Because of the wide spectrum of collected information, the National Register represents a useful tool for developing of collaborative studies concerning some aspects of CH not yet completely elucidated.

[Peripheral androgen resistance syndrome]. / Le sindromi da resistenza periferica agli androgeni.

Two main topics of 5 alpha reductase deficiency and androgen receptors defects have been considered. Particularly, the differential diagnosis among the different syndromes of androgen resistance and the important issue of sex assignment are discussed.

[Primary pulmonary hypertension in childhood: familial aspects]. / Ipertensione polmonare primitiva (I.P.P.) nell'infanzia: familiarità.

Primary pulmonary hypertension (PPH) is a rare, progressive and usually fatal disease. Its pathogenesis remains obscure. Probably multiple genetic and environmental factors play a role in the occurrence of PPH. PPH sometimes runs in families. We have studied two families in which some members were affected: in family A two sibs, their father and probably their paternal grandmother, in family B two sibs. When PPH is present in more than one generation (family A), an autosomal dominant mode of inheritance would be likely, whereas, when the disease is present in only one generation (family B), an autosomal recessive mode of inheritance is more probable. Treatment of PPH is based on pulmonary vasodilator drugs, because one of the most important mechanisms is thought to be an inappropriate vasoconstriction. Some drugs like oxygen, tolazoline, acetylcholine, isoproterenol seem to get poor results, while phentolamine, nifedipine, hydralazine and diazoxide show promise. Diazoxide appears to have some advantages because it reduces not only pulmonary arteriolar resistance, but also pulmonary artery pressure, without producing tachycardia.

[Yersinia enterocolitica infection in thalassemia. Report of one case (author's transl)]. / L'infezione da Yersinia enterocolitica in corso di talassemia mayor. Descrizione di un caso.

The Authors describe a rare case of Yersinia Enterocolitica (Y.E.) infection in a child affected by thalassemia. The onset of the disease was that of an acute enteritis with diarrhea, fever, vomiting and abdominal pain which subsequently evolved in a picture consistent with an acute appendicitis. Laparotomy was then performed and showed a marked suppurative mesenterial lymphadenitis with mild appendicular inflammation and Y.E. infection was suspected. Culture from lymphonodes confirmed the presence of Y.E. sensitive to tobramicin and CTM. The use of these chemiotherapic agents has been followed by a rapid clinical improvement. Our recent experience could suggest some practical considerations: 1) Culture of Y.E. should be routinely performed in all children affected by acute gastroenteritis and particularly in those, above 5 years of age, in which the infection can simulate acute appendicitis. 2) Special attention should be carried out in children affected by thalassemia who can easily present more serious disease often complicated by septicemia. 3) Therapy depends on the form and severity of the disease and should be always guided by in vitro sensitivity test because of the possibility of resistence of Y.E. against the most frequently used antibiotics in septicemia.

[Hemodynamic study of pulmonary vascular resistances in subjects with Down's syndrome with atrioventricular canal]. / Studio emodinamico delle resistenze vascolari polmonari in soggetti Down con canale atrioventricolare.

Down patients frequently present congenital heart disease (CHD). Among these the most common is complete atrioventricular canal (CAV). The Authors studied by cardiac catheterization 2 groups of subjects with CAV:21 Down-patients, aged 5-48 months (mean = 24.7) and 17 non-Down patients aged 6-50 months (mean = 23.1). Hemodynamic data were compared and in particular pulmonary vascular resistances (PVR) were analysed. Mean pulmonary resistance was 11.1 UM2 for Down children and 4.6 UM2 for non-Down children. Considering the subjects under 2 years of age, PVR greater than or equal to 10 UM2 was present in 5 of 14 (35.7%). Down children, while none in the non-Down group. The cause of this behaviour is unknown; some Authors, in pathological studies, found in Down-patients primitive structural anomalies of the vascular bed with decrease of total vascular surface area. This fact might explain higher values of PVR in Down-patients than in non-Down patients.

[Treatment by human chorionic gonadotropin in maldescended testes. (Synthesis of our experience)]. / Il trattamento del criptorchidismo con gonadotropina corionica (Sintesi della nostra esperienza).

87 prepuberal children, 2-15 years old, 58 with unilateral and 29 with bilateral cryptorchidism, were treated intramuscularly with Human Chorionic Gonadotropin (HCG). HCG was administered in 16 children in single dose (5.000 IU/m2), in 11 children every other day for one week (3 x 1,500 IU) and in 60 children twice a week (2 x 1,000 IU) for 3-7 weeks. Treatment was successful in 31% of children. The most effective HCG dosage ranged between 10,000 and 14,000 IU (2 x 1,000 IU once a week for 5-7 weeks). The best therapeutic response was obtained in inguinal cryptorchid testes (39,3%), in unilateral cryptorchidism (34,5%) and in children aged 5-10 years (42,3%). The observed androgenic side effects (32%) subsided within 3-12 months after therapy suspension. The HCG therapy appears of particular value in cryptorchidism treatment. Surgical management is indicated in cases of true ectopic testes and after failure of HCG therapy.

Ovarian hydatid cyst: A case report.

Discovering an hydatid cyst in pelvic region, especially as primary localization, is a rare event; as a matter of fact according to data provided by literature the incidence is between 0.2 and 2.25%. The ovarian involvement is often secondary to a cyst's dissemination localized in a different site. When possible the optimal treatment is represented by radical laparotomic cystectomy. We report a case of an old woman affected by this pathology that we have treated with a cyst's marsupialization after a draining and irrigation of cyst cavity with hypertonic saline solutions.