Pineal germinoma in a child with interferon-γ receptor 1 deficiency. case report and literature review.

Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report the first case of intracranial tumour, i.e. pineal germinoma, in a 11-year-old patient with complete IFN-γR1 deficiency. The first clinical presentation of the genetic immunodeficiency dates back to when the child was aged 2 y and 10 mo, when he presented a multi-focal osteomyelitis caused by Mycobacterium scrofulaceum. The diagnosis of IFN-γR1 deficiency (523delT/523delT in IFNGR1 gene) was subsequently made. The child responded to antibiotic therapy and remained in stable clinical condition until the age of 11 years, when he started complaining of frontal, chronic headache. MRI revealed a solid pineal region mass lesion measuring 20 × 29 × 36 mm. Histological findings revealed a diagnosis of pineal germinoma. The patient received chemotherapy followed by local whole ventricular irradiation with boost on pineal site, experiencing complete remission, and to date he is tumor-free at four years follow-up. Four other cases of tumors have been reported in patients affected by MSMD in our knowledge: a case of Kaposi sarcoma, a case of B-cell lymphoma, a case of cutaneous squamous cell carcinoma and a case of oesophageal squamous cell carcinoma. In conclusion, in patients with MSMD, not only the surveillance of infectious diseases, but also that of tumors is important.

Caffeine consumption among eating disorder patients: epidemiology, motivations, and potential of abuse.

OBJECTIVE: Aim of the study was to investigate caffeine use in different types of eating disorders (ED) patients either using a categorical approach [Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM-IV-TR) diagnostic criteria] or a dimensional perspective. METHOD: Fifty-eight ED female patients [anorexia nervosa (AN), restricting and binge-eating/purging type, N=15; bulimia nervosa (BN) purging type/nonpurging type, N=26; binge eating disorder (BED), N=17] referred to an Eating Disorder Unit and 15 non-clinical controls were administered the Eating Disorder Inventory-2 (EDI-2), the Clinical Global Impression (CGI) and the Caffeine Use Test, an interview specifically developed to investigate caffeine intake. Statistical analyses were then repeated clustering patients according to the presence/absence of purging behaviors (purgers, N=22; non-purgers, N=19; BED, N=17). RESULTS: Current and lifetime caffeine use, measured as mg/day, were similar comparing controls and ED patients as a whole. BN patients showed a significantly higher maximum lifetime caffeine intake (817.4+/-528,9 vs 325.0+/-294.6 mg/die, F=3.246, p<0.05); the same for purgers vs controls (p<0.05). Caffeine abuse was significantly more represented among patients vs controls (p<0.01), but similar among different patients' groups. As for diagnoses according to DSM-IV-TR Substance Use modified for caffeine, no significant difference was found among the different groups, for either Dependence, Intoxication or Withdrawal. Most of patients and controls reported pleasure as the main motivation for caffeine use, followed by increased vigilance and attention and appetite suppression in AN and BN patients. Note that a shift in diagnosis in the course of the ED from non-purging to purging type was associated with an increase in caffeine current, lifetime and maximum lifetime intake (F=1.667 p<0.05), except for BED patients. Severity of the ED measured as CGI score or comorbidity did not affect caffeine intake in patients as a whole, but in the purging subgroup current caffeine use was increased in presence of an anxiety disorder (p<0.05), and decreased in presence of a mood disorder (p<0.01). CONCLUSIONS: Data from the present study are in agreement with previous evidence in literature that a high percentage of ED patients ordinarily use caffeine with an average intake similar to that of the general population, however with a kind of binge attitude. Among heavy drinkers, daily caffeine intake and alcohol/cigarettes use are associated supporting the link with the dimension of impulse disregulation. The substantial number of subjects from our sample satisfying research criteria for Dependence, together with increasing reports of caffeine intoxication, suggests the growing relevance of these issues that deserve further investigation.

Intracranial aneurysm associated with chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis (CMC) is a syndrome characterised by immune deficiency, often presenting familial dominant inheritance and association with autoimmune endocrinopathies. We report on a patient with CMC who died at 5 years of age of a brain haemorrhage following the rupture of a basilar-artery aneurysm. Candida hyphae in the basilar artery were found at autopsy. A common immunologic abnormality in CMC is the failure of patient's T-lymphocytes to produce cytokines, which are essential for expression of cell-mediated immunity to Candida. Therefore, long-term treatment is mandatory.

Varicella and its complications as cause of hospitalization.

Varicella is an acute contagious disease that most commonly occurs in childhood. Although normally benign, varicella can occasionally develop into a more serious illness. Moreover, the infection can lead to serious complications, such as Staphylococcus aureus infections, otitis media, endocarditis, pneumonia, and rare central nervous system (CNS) events like cerebellar ataxia and encephalitis. This study was conducted to analyze the hospitalization rate due to varicella or its complications in a tertiary care hospital in Italy, where varicella vaccination has not yet been implemented. The review was carried out on cases of children with varicella identified by ICD9 and ICD9-CM diagnostic codes and admitted to the Giannina Gaslini Children's Research Hospital of Genoa, Italy, from January 1st, 1995 to December 31st, 2004. For each case reporting complications, the clinical report form was extracted and the events recorded. Varicella was recorded in 346 (0,16%) out of 212,647 total hospital discharges. Chickenpox with detailed complications and cerebrovascular diseases accounted for 56 discharges (12.14%), for a total of 728 days. Fifteen patients needed more than one hospitalization because of severe sequelae as result of CNS involvement. We reported three particular cases of invasive infections and four children affected with cerebrovascular diseases following varicella. Our retrospective data regarding a single tertiary care pediatric hospital shows that hospitalization due to varicella or its sequelae may present an important medical and indirect economic problem.

Scleromyxedema: successful treatment of cutaneous and neurologic symptoms.

Scleromyxedema is a rare systemic disorder characterized by cutaneous sclerosis and papulosis, accompanied by deposition of mucin in the skin and other organs. We describe a case of scleromyxedema in a 62-year-old man. The cutaneous symptoms of the disorder were preceded by episodes of acute central nervous system dysfunction that included mental confusion, hemiparesis, tremor, and migraine. As the cutaneous symptoms progressed, the patient experienced persistent confusion and difficulty concentrating. Therapy with melphalan and plasmapheresis led to complete resolution of the cutaneous symptoms as well as near-resolution of the neurologic symptoms. This is the first report to describe the successful treatment of the cutaneous symptoms of scleromyxedema accompanied by reversal of chronic neurologic dysfunction.

Clinical and biological characteristics of immunopathological disease-related erythema nodosum in children.

We report a series of 22 children with idiopathic, drug unrelated erythema nodosum (EN) admitted to our Department. In 5 of them an history of streptococcal pharyngitis was referred; the remaining patients came to us with a diagnosis of "EN of unknown origin". Acute phase reactants, immunoglobulins, stool alpha1 antitrypsin, ANA, anti dsDNA antibodies and ANCA assay, chest roentgenogram, tuberculin test, and ophthalmologic assessment were performed in all patients. Etiologic diagnosis was made in 16 patients: Streptococcal pharyngitis (5 cases), chronic inflammatory bowel disease, IBD (3 cases), Behçet syndrome (2 cases), Yersinia enteritis (2 cases), infectious mononucleosis, atypical mycobacterial infection, immunodeficiency related infection, and SLE-like syndrome due to C4 deficiency (1 case each). We found oral/scrotal aphthae in 3 cases, gastrointestinal symptoms in 5 cases, arthritis in 3 cases. Acute phase reactants were positive in 16 patients without correlation to the underlying disease. Conversely, the increased alpha1 antitrypsin stool excretion and IgA serum concentration seemed to represent helpful indicators of IBD and Behçet syndrome, respectively. Proinflammatory cytokine pattern showed increased IL6 serum concentrations both in infectious and in non infectious disease-related EN, whereas a minor involvement of TNF was found in these patients.

Differential dynamic responses of luteinizing hormone to gonadotropin releasing hormone in patients affected by bulimia nervosa-purging versus non-purging type.

OBJECTIVE: Aim of the study was to investigate the presence of underlying abnormalities affecting the hypothalamus-pituitary-gonadal axis in 13 normal weight eumenhorreic bulimics as expressed by a different gonadotropin response to gonadotropin releasing hormone (GnRH), comparing patients with (n = 6) and without (n = 7) purging behaviours to controls (n = 5). METHOD: Subjects were administered an intravenous GnRH infusion for four hours, with an additional bolus at first and third hour. RESULTS: Non-purging bulimics showed a significantly reduced luteinizing hormone (LH) response to GnRH compared to controls; purging bulimics, following the second bolus, demonstrated a statistically reduced peak, in comparison to both controls and non-purging bulimics. DISCUSSION: even in the absence of overt menstrual disturbances, an altered LH secretion elicited by pulsatile stimulation of endogenous GnRH was found, with a more severe impairment in purging than in non-purging bulimics, possibly related to their greater psychopathological and physical burden.

Local antimicrobial therapy of oral mucositis in paediatric patients undergoing bone marrow transplantation.

The present investigation has examined the clinical benefits of tobramycin, polymyxin E and amphotericin therapy in the management of oral mucositis in children undergoing chemotherapy prior to bone marrow transplantation. Tobramycin, polymyxin E, and amphotericin reduced the degree of oral mucositis more than conventional therapy of diphenhydramine, Maalox, and local analgesic. While there was a statistically significant fall in the severity of the mucositis with tobramycin, polymyxin E and amphotericin, this was unlikely to be of practical benefit.

Ulcerated necrobiosis lipoidica diabeticorum in a patient with a history of generalized granuloma annulare.

Granuloma annulare and necrobiosis lipoidica diabeticorum have rarely been reported in the same patient. We describe the unusual case of a woman with diabetes and a history of generalized granuloma annulare who noted leg ulcers that clinically represented ulcerated necrobiosis lipoidica diabeticorum and had histologic features of necrobiosis lipoidica diabeticorum and granuloma annulare. Her condition responded to treatment with antiplatelet agents.

A rare malposition of the central venous catheter.

The left pericardiacophrenic vein was accidentally cannulated during an attempt to establish central venous catheterization through the left internal jugular vein. Chest roentgenograms and intravenous contrast material confirmed the position of the catheter. Although our patient developed no problems during a five-day cannulation, based on published information, it is advisable to reposition the catheter to avoid perforation of the pericardiacophrenic vein and possible cardiac tamponade.

Peptides related to the calcium binding domains II and III of calmodulin. Synthesis and calmodulin-like features.

Three hexadecapeptides which correspond to the putative Ca2+ binding domains II and III of calmodulin were synthesized employing solid phase methodology. One of the peptides contained an internal cystine bridge which was formed while the corresponding linear peptide was still attached to the polymeric carrier. The interaction of the synthetic peptides with calcium ions was investigated using Tb3+-mediated fluorescence. Binding was of the order Ca12 greater than Ca13 greater than Ca13C (Fig. 1) with binding constants KTb3+ = 0.68 X 10(-5), 0.54 X 10(-5), and 0.21 X 10(-5) M-1 respectively. Biological activity of the compounds was assessed by measuring their stimulatory effect on erythrocyte membrane (Ca2+ + Mg2+)-ATPase activity. For 50% activity as compared with CaM, the concentration of peptides required was for Ca12, Ca13 and Ca13C, 50, 100 and 167 times higher than CaM, respectively. The results suggest that the three synthetic peptides possess certain calmodulin-like features.

Human cutaneous nevi transplanted onto nude mice: a model for the study of the lesional steps in tumor progression.

Normal human cutaneous nevi were transplanted to the skin of nude mice and some of the grafts were treated topically with 7,12-dimethylbenz[a]anthracene (DMBA, 1.6 mumol weekly). Histologically proven human skin was present in 22 grafts. In the 9 untreated control grafts, the tendency of nevic cells to form nests and the number of nevomelanocytes decreased with time; the melanocytic cells showed no signs of hypertrophy or atypia. In most of the 14 specimens treated with DMBA, the nevomelanocytes showed distinct signs of hypertrophy. The cells were enlarged and often dendritic and were filled with melanin granules for which the transfer to keratinocytes appeared to be blocked. The nevomelanocytes of 4 of the 9 specimens treated with DMBA for greater than or equal to 82 days (9-16 DMBA applications), showed atypical enlarged nuclei with mitotic figures. Since atypia is one criterion for identifying precursors of transformed cells, the model of human nevi grafted onto nude mouse skin may be useful for studying the various steps involved in the progression of benign melanocytic nevi to malignant melanoma.

Characteristics of cultured human melanocytes isolated from different stages of tumor progression.

Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.