"Assessing Today for a Better Tomorrow": An observational cohort study about quality of care, mortality and morbidity among newborn infants admitted to neonatal intensive care in Guinea.

BACKGROUND: Neonatal mortality in Guinea accounts for about 30% of all fatalities in children younger than five years. Countrywide, specialized neonatal intensive care is provided in one single clinic with markedly limited resources. To implement targeted measures, prospective data on patient characteristics and factors of neonatal death are needed. OBJECTIVE: To determine the rates of morbidity and mortality, to describe clinical characteristics of admitted newborns requiring intensive care, to assess the quality of disease management, and to identify factors contributing to neonatal mortality. METHODS: Prospective observational cohort study of newborns admitted to the hospital between mid-February and mid-March 2019 after birth in other institutions. Data were collected on maternal/prenatal history, delivery, and in-hospital care via convenience sampling. Associations of patient characteristics with in-hospital death were assessed using cause-specific Cox proportional-hazards models. RESULTS: Half of the 168 admitted newborns underwent postnatal cardiopulmonary resuscitation. Reasons for admission included respiratory distress (49.4%), poor postnatal adaptation (45.8%), prematurity (46.2%), and infections (37.1%). 101 newborns (61.2%) arrived in serious/critical general condition; 90 children (53.9%) showed clinical signs of neurological damage. Quality of care was poor: Only 59.4% of the 64 newborns admitted with hypothermia were externally heated; likewise, 57.1% of 45 jaundiced infants did not receive phototherapy. Death occurred in 56 children (33.3%) due to birth asphyxia (42.9%), prematurity (33.9%), and sepsis (12.5%). Newborns in serious/critical general condition at admission had about a fivefold higher hazard to die than those admitted in good condition (HR 5.21 95%-CI 2.42-11.25, p = <0.0001). Hypothermia at admission was also associated with a higher hazard of death (HR 2.00, 95%-CI 1.10-3.65, p = 0.023). CONCLUSION: Neonatal mortality was strikingly high. Birth asphyxia, prematurity, and infection accounted for 89.3% of death, aggravated by poor quality of in-hospital care. Children with serious general condition at admission had poor chances of survival. The whole concept of perinatal care in Guinea requires reconsideration.

Clinical presentation and improvised management of neonatal pneumothorax in the setting of a low-resource country: Conakry, Guinea.

Two neonates were presented at the Neonatology Department of the Institute of Child Nutrition and Health in Conakry, Guinea, with tension pneumothoraces as confirmed by chest X-ray. They were initially managed with needle thoracentesis but required continuous thoracic drainage. Due to scarce resources in the public health sector, no prepacked and dedicated pleural drainage systems were available as is the case in many developing countries. Therefore, we fabricated an improvised underwater seal drain out of a plastic infusion bottle and a Heimlich valve out of a vicryl fingerstall. Both devices have shown to be effective. Pneumothorax is a common and potentially life-threatening disease in neonates that often requires prompt treatment. This case series demonstrates how tension pneumothorax in two newborns was successfully managed by improvising different chest drainage systems. The depicted techniques shall serve as an instruction manual to healthcare professionals working in low-resource settings and facing similar challenges.

Nutritional status of people living with HIV/AIDS in the Ratoma community medical center (Republic of Guinea).

The nutritional status of people living with HIV/AIDS (PLHIV) has a direct impact on their health. The aim of this study was to describe the nutritional status of PLWHA receiving care at the Ratoma community medical center in Conakry, Guinea. This quantitative cross-sectional study assessed the nutritional status of 184 people PLHIV receiving antiretroviral treatment. The sample comprised 184 PLHIV selected by a systematic random sampling from the complete list of PLHIV. The data were collected by individual questionnaires. Two groups were defined according to their nutritional status, based on their body mass index (BMI): a malnourished group (BMI < 18,5kg/m2) and a well-nourished group (BMI ≥ 18,5kg/m2). CD4 lymphocyte counts were also collected. Of the 184 PLVIH, 19.6% were malnourished (95%CI: 14.1-25.0). The mean BMI was 22.2 ± 4.3 kg/m2). The mean CD4 count differed significantly between the groups (328.7±237.7 CD4 cells/mm3 for the malnourished group and 432.9±256.9 for the well-nourished, p <0.017). Malnutrition was significantly associated with a low CD4 count. To improve survival and quality of life among PLHIV, this high frequency of malnutrition calls for sustained attention to the prevention and early detection and treatment of malnutrition in the early stages of HIV.

Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.

Loss of Rassf1a cooperates with Apc(Min) to accelerate intestinal tumourigenesis.

Promoter methylation of the RAS-association domain family 1, isoform A gene (RASSF1A) is one of the most frequent events found in human tumours. In this study we set out to test the hypothesis that loss of Rassf1a can cooperate with inactivation of the adenomatous polyposis coli (Apc) gene to accelerate intestinal tumourigenesis using the Apc-Min (Apc(Min/+)) mouse model, as mutational or deletional inactivation of APC is a frequent early event in the genesis of intestinal cancer. Further, loss of RASSF1A has also been reported to occur in premalignant adenomas of the bowel. RASSF1A has been implicated in an array of pivotal cellular processes, including regulation of the cell cycle, apoptosis, microtubule stability and most recently in the beta-catenin signalling pathway. By interbreeding isoform specific Rassf1a knockout mice with Apc(+/Min) mice, we showed that loss of Rassf1a results in a significant increase in adenomas of the small intestine and accelerated intestinal tumourigenesis leading to the earlier death of adenocarcinoma-bearing mice and decreased overall survival. Comparative genomic hybridization of adenomas from Rassf1a(-/-); Apc(+/Min) mice revealed no evidence of aneuploidy or gross chromosomal instability (no difference to adenomas from Rassf1a(+/+); Apc(+/Min) mice). Immunohistochemical analysis of adenomas revealed increased nuclear beta-catenin accumulation in adenomas from Rassf1a(-/-); Apc(+/Min) mice, compared to those from Rassf1a(+/+); Apc(+/Min) mice, but no differences in proliferation marker (Ki67) staining patterns. Collectively these data demonstrate cooperation between inactivation of Rassf1a and Apc resulting in accelerated intestinal tumourigenesis, with adenomas showing increased nuclear accumulation of beta-catenin, supporting a mechanistic link via loss of the known interaction of Rassf1 with beta-TrCP that usually mediates degradation of beta-catenin.

Sperm aneuploidy and recurrent pregnancy loss.

Experiments of double target in-situ hybridization were performed separately for chromosomes 1-17, 8-18 and sex chromosomes on sperm samples from 20 couples suffering from three or more recurrent first trimester abortions. For a subset of this study population, additional experiments of multicolour fluorescence in-situ hybridization for chromosomes 4, 7, 12, 13, 15, 18, 21, and 22, were performed on the bases of the available data from abortive tissue karyotyping. A markedly high rate of sperm disomy (14.5-15.5%) was scored in only two cases. For three other patients, the cumulative disomy rates for chromosomes 1, 17, 8, 18, X and Y also increased but at a lower level (7.8-9.5%). For the remaining 15 patients, the frequency of sperm aneuploidy was moderately increased or normal. Men with recurrent pregnancy loss (RPL) and poor semen quality had baseline sperm aneuploidy and diploidy rates higher than men with normal semen parameters (with or without RPL). Using probes for chromosomes 1, 17, 8, 18, X and Y, significantly elevated frequencies of sperm aneuploidy (not diploidy) were found in 10% of men with a history of RPL. Their rate of sperm aneuploidy was 30-34%. For the other men, changes in sperm aneuploidy were not thought to affect RPL. Poor semen quality per se impacted negatively on sperm aneuploidy and diploidy, thus making the interpretation of clinical data more difficult.

Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling.

Knowledge of the impact of different conditioning regimens used in bone marrow transplantation on spermatogenesis is important in pre-BMT counselling for three reasons: (1) Most young patients who have not had children are concerned with their subsequent fertility; (2) For a number of diseases there are competing therapeutic options that may affect spermatogenesis more or less seriously; (3) Since spontaneous recovery of spermatogenesis is rare, it would be necessary to offer cryopreservation as soon as possible after diagnosis and prior to any treatment. This retrospective study evaluates 99 semen samples obtained in 64 patients who underwent BMT between 1982 and 1996. Recovery of spermatogenesis was observed in 90% of patients conditioned with cyclophosphamide (CY), in 50% of patients with CY plus busulphan (BU) or thiotepa and in 17% of patients with CY plus total body irradiation (TBI) or thoracoabdominal irradiation (TAI). Sperm quality following CY was within the normal range (WHO) in the majority of patients, whereas it was consistently severely impaired in patients who received irradiation or two alkylating agents. Following CY, spermatogenesis recovery was observed in 60% of patients tested 1 year post transplant and it was accomplished within the third year in 80% of cases. Following CY + TBI/TAI recovery of spermatogenesis never occurred before the 4th year post transplant and was demonstrated as late as 9 years in one patient who was azoospermic 1 year earlier. No statistical correlation between age and recovery of spermatogenesis could be demonstrated. The overall high incidence of azoospermia (70.3%) supports the indication for semen cryopreservation in young patients undergoing BMT. These results have implications for semen sample timing before and after BMT and underline a need to collect further data through prospective multi-center studies.

Pituitary adenomas in childhood and adolescence. Clinical analysis of 10 cases.

Pituitary adenomas in childhood and adolescence constitute 2-6% of all operated pituitary adenomas. We report the clinical features, treatment and follow-up of 10 pediatric patients affected by pituitary adenomas. All patients underwent clinical evaluation, endocrine tests, magnetic resonance imaging and visual field assessment. Follow-up ranged from 8 to 132 months (median 52.6). All patients were older than 10 years of age; 60% were males. In 50% the initial complaints were headache and/or visual impairment, all except one had clear evidence of endocrine dysfunction. Ninety percent were macroadenomas. According to hormone measurements and immunostaining 50% were prolactinomas, 20% were pure GH-secreting and 30% were non-functioning adenomas. Prolactinomas in two females were successfully treated with cabergoline. The other patients underwent surgery: three prolactinomas are still being treated with dopamine agonists and a GH-secreting adenoma is being treated with octreotide LAR and cabergoline. Two patients were also treated with conventional radiotherapy. Treatments were completely successful in 50% of patients: these have normal hormone secretion, full pubertal development, no significant tumor mass and normal visual field. Hypersecretion of prolactin persists in two cases; partial or complete hypopituitarism is present in four, relevant tumor remnant in another four and impairment of visual field is present in two cases. In conclusion, pediatric adenomas occur mostly in pubertal age, are prevalently macroadenomas and clinically functioning. Medical therapy should be preferred for secreting adenomas, but in some cases, notably prolactinomas in males, surgery and eventual radiotherapy may be needed.

Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and testicular germ cells of infertile patients.

The hypothesis that sperm aneuploidy and diploidy increase as a function of spermatogenesis impairment was addressed. Ejaculated semen samples from a series of men (n = 22) with very low total normal motile count (1 x 10(6)) was analysed in terms of sperm aneuploidy and diploidy by in-situ hybridization and compared with controls (n = 10). Germ cell aneuploidy was also analysed in an additional series of infertile patients presenting unexplained infertility (n = 3), congenital absence of the vas deferens (CAVD) (n = 6) and non-obstructive azoospermia (n = 3) undergoing IVF, microsurgical epididymal sperm aspiration (MESA)/ICSI and testicular sperm extraction (TESE)/ICSI cycles respectively. In-situ hybridization for chromosomes 1, 17, X and Y was performed on ejaculate, epididymal and testicular spermatozoa. Significantly higher sperm aneuploidy and diploidy rates where found (for the four chromosomes analysed) in spermatozoa from oligoasthenoteratozoospermia (OAT) over controls (18 versus 2.28% and 2.8 versus 0.13% respectively; P < 0.001). Testicular germ cells had even higher rates of sperm aneuploidy and diploidy. However, in this group it was difficult to determine whether the cells analysed were dysmorphic spermatozoa or spermatids. The data warrant further investigation on the cytogenetic abnormalities found in most germ cells identified in testicular tissue biopsies of azoospermic patients.

Translocation and coamplification of loci from chromosome arms 8p and 11q in the MDA-MB-175 mammary carcinoma cell line.

Rearrangement and coamplification of the 8p12 and 11q13 chromosomal regions occurs in a significant proportion of breast cancers. It usually involves a complex hybrid structure in which the FGFR1 and CCND1 genes are amplified. We report here a different type of 8p12-11q13 rearrangement in the MDA-MB-175 mammary carcinoma cell line. This amplification contains the NRG1/HGL (from 8p12-21) and DOC4 (from 11q13) genes, encoding respectively a ligand for ERBB receptors and a stress-induced protein which is a mammalian ortholog of Drosophila Tenm/Odz. It has been shown previously (Wang et al, Oncogene 18: 5718-5721, 1999) that these two genes are rearranged and fused by a translocation event. This type of event was not found in 30 tumors tested that showed coamplification of the 8p12 and 11q13 regions.

gamma-heregulin is the product of a chromosomal translocation fusing the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell line.

gamma-heregulin is a recently described novel isoform of the heregulin/neuregulin class of EGF-like ligands that bind to and activate receptors of the ErbB family. Deregulated signaling through the heregulin-ErbB pathway is thought to be implicated in the development of a subset of human breast cancers. gamma-heregulin has been found to be expressed in the culture supernatant of MDA-MB-175, a breast carcinoma cell line. gamma-heregulin is characterized by the presence of a large N-terminal peptide extension that is not found in other heregulin isoforms. Here we report that this unique N-terminal extension of gamma-heregulin is identical to the N-terminus of DOC4, a product of a recently identified CHOP-dependent stress-induced gene. Human DOC4 and the heregulin-encoding genes map to different chromosomes and the MDA-MB-175 cell line contains a chromosomal translocation that leads to the fusion of DOC4 and HGL, on chromosomes 11 and 8, respectively. Thus, gamma-heregulin is a product of a mutant fusion gene and not a bona fide normal isoform. We speculate that the mutation may be selected for by virtue of its ability to activate ErbB signaling through the production of an autocrine ligand.

Danazol and multiple hepatic adenomas: peculiar clinical findings in an acromegalic patient.

Hepatic adenomas are rare tumors; they have been associated with the use of anabolic steroids. Acromegaly increases the overall risk of neoplasms. We report the case of a female acromegalic patient in whom multiple hepatic adenomas appeared soon after danazol treatment for uterine fibromatosis. Treatment of acromegaly with octreotide, followed by successful selective pituitary adenomectomy, stabilized the number and the size of the liver tumors. We suggest that oversecretions of GH and IGF-I were strong promoting factors for liver tumorigenesis in this patient.

[The timing in differential diagnosis of cystic tumors of the pancreas: clinical report of three cases of cystadenocarcinoma]. / Il "timing" nella diagnosi differenziale dei tumori cistici del pancreas: contributo clinico su tre casi di cistoadenocarcinoma.

The Authors analyze their own twelve-years experience about the Cystic Tumors of the Pancreas, considering the data existing in the literature. In particular, after a description of anatomo-pathological and clinical characteristics, they set out the problems in the differential diagnosis between the Cystadenocarcinomas and the other benign cystic lesions of the Pancreas. The solution of this problem is often reached only during the operation with multiple biopsies. Moreover they pay attention to the therapeutic choices, determined by the symptomatology of the patients and the localization and the histological kind of the lesions.

Study of aneuploidy in normal and abnormal germ cells from semen of fertile and infertile men.

This study was undertaken with the aim of investigating the cytogenetic constitution of normal as well as abnormal spermatozoa and immature germ cells found in semen of normal men and infertile patients. A specific protocol of double in-situ hybridization for chromosomes 1 and 17 based on colorimetric detection of the hybridization signals (ISH) and brightfield microscopy analysis of cellular morphology was applied. Also the influence of paternal age on sperm aneuploidy was investigated. We found that, at least in the age range analysed (28-54 years) and for semen of good quality (total normal motile counts above 10 x 10(6)) (n = 17), paternal age has no influence on baseline rates of sperm aneuploidy. However, with decreasing semen quality (total normal motile sperm counts below 5 x 10(6)) (n = 6) significantly higher rates of sperm aneuploidy for autosomes 1 and 17 were scored (0.8 versus 1.43%) (P < 0.001). Regardless of the type of semen analysed, a number of morphologically abnormal spermatozoa were found to be hyperhaploid or diploid in a high percentage of cases (20 and 10% respectively). The same was found for immature germ cells (aneuploidy rate of 18%). We conclude that in infertile men with poor quality semen a direct relationship may exist between the impairment of the spermatogenesis process (as reflected by an increased production of morphologically and cytogenetically abnormal germ cells) and rates of baseline aneuploidy occurring in normal spermatozoa. Infertile couples undergoing assisted reproduction treatment need to be counselled about the risk of using spermatozoa which may carry higher rates of non-disjunction for different chromosomes. While sperm hyper- or hypohaploidy for some chromosomes (X,Y) implies counselling couples about the risk of abnormal phenotype in their offspring, most autosomal sperm aneuploidies probably translate only into lower rates of embryo fertilization and survival.

[A case of anaplastic thyroid carcinoma]. / Un caso di carcinoma anaplastico della tiroide.

The Authors report a case of anaplastic thyroid carcinoma surviving more than 20 months from the time of diagnosis and still living. The patient underwent surgery (total thyroidectomy), chemotherapy (cisplatin and doxorubicin according to Schlumberger), and radiotherapy (5000 Gy).

Potential of endocervical lavage for cytogenetic investigation of fetal cells as determined by in situ hybridization.

Aims: Transcervical samples following endocervical lavage from 28 women undergoing pregnancy termination were analysed in terms of fetal cells content and suitability for in situ hybridization analysis. A non fluorescent protocol of hybridization coupled to specific cytological procedures was used for simultaneous recognition and investigation on syncitiotrophoblast fragments. Methods: A series of endocervical washings was randomised to cytobrushing samples. Cervical washings were performed using variable volumes of physiologic saline solution (2ml, 5ml, 10ml). Single target in situ hybridization for chromosomes 1 and 18 was applied for determining a model of efficiency. Syncitial cells were recognized by means of cytoplasmic and nuclear stainings obtained with Eosin G (Diff-Quik) and haematoxylin respectively. Results: When 5 - 10ml of sterile solution were flushed multiple fragments of syncitio-trophoblast were almost constantly recovered. Conversely using 2ml of flushing solution no syncitia at all could be retrieved. Fetal cells were collected only in 50% of cervical cytobrushing. The per cell hybridization efficiency was on average 50%. Following in situ hybridization, a normal number of signal-products (2) was found in all nuclei analysed. Conclusion: During endocervical washing the amount of volume used is a critical factor to allow successful recovery of fetal cells. By using 5 - 10 ml of injecting solution, enough fetal material was generally obtained from each individual to guarantee the cytogenetic investigation for two chromosomes. The use of Diff-Quik and haematoxylin staining coupled to bright-field microscope facilitate the recognition of syncitia among a highly heterogeneous population of maternal cells. Further studies are ongoing to prospectively evaluate safety of the transcervical approach for sampling and analysis of fetal cells.

Long-term effects of octreotide on markers of bone metabolism in acromegaly: evidence of increased serum parathormone concentrations.

The effects of octreotide on biochemical markers of bone turnover were evaluated in patients with active acromegaly. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before and after 4 months of treatment in 27 patients (short-term treatment) and after 12 and 24 months of treatment in 15 patients (long-term treatment). In the short-term, octreotide significantly decreased the levels of serum GH, IGF-I, calcium, osteocalcin, carboxyterminal propeptide of type I collagen and alkaline phosphatase plus urinary excretion of calcium. Short-term treatment significantly increased serum parathormone levels (before treatment 30.1 +/- 9.57 and at 4 months 46.1 +/- 24.98 ng/L, p < 0.001) and urinary excretion of phosphate; urinary excretion of hydroxyproline was unchanged. The same results were observed during long-term treatment, except that there was no significant difference of serum calcium and alkaline phosphatase levels before and after treatment. Parathormone concentrations were still higher at 24 months compared with those prior to treatment (before treatment 31.9 +/- 9.74 and at 24 months 44.9 +/- 21.18 ng/L, p < 0.05). The changes of most bone markers during octreotide therapy can be explained by the decrease of serum GH and IGF-I concentrations. On the other hand, the rise of parathormone concentrations suggests that octreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the octreotide could contribute to this secondary hyperparathyroidism. The clinical consequences of these alterations of bone metabolism need to be further clarified.

111Indium-pentetreotide pituitary scintigraphy and hormonal responses to octreotide in acromegalic patients.

GH secreting pituitary adenomas are frequently visualized by scintigraphy with the somatostatin analogue 111Indium-pentetreotide. We studied 111Indium-pentetreotide scintigraphy and hormonal responses to octreotide in 12 acromegalic patients. Nine patients with active acromegaly were studied before pituitary adenomectomy; 6 of these and 3 other patients were studied after operation. GH was measured after a single s.c. dose of 100 micrograms of octreotide (acute test). The patients were preoperatively treated with 100 micrograms s.c. tid octreotide for 3 months as were patients who had been unsuccessfully operated; GH and IGF-I were measured at the end of this period (chronic treatment). A decrease of the hormones higher than 50% of basal values was considered a positive response in both acute test and chronic treatment. Eight/nine unoperated patients had a pituitary adenoma visualized by scintigraphy and a positive response to both the acute test and chronic treatment; one patient had no evidence of tumor at scintigraphy and he did not respond to octreotide. Scintigraphy was negative in all of the three patients cured by surgery. Six patients still had active disease after adenomectomy: scintigraphy was positive only in one case, although GH responded to octreotide treatment in all patients. Conclusions. 111In-pentetreotide scintigraphy frequently visualizes pituitary adenomas and predicts GH responses to octreotide in unoperated acromegalic patients. In unsuccessfully operated patients scintigraphy is infrequently positive and does not predict which patients will respond to octreotide. These data and the cost of 111In-pentetreotide scintigraphy do not warrant its extensive clinical use in acromegaly.

Comparison of gonosomal aneuploidy in spermatozoa of normal fertile men and those with severe male factor detected by in-situ hybridization.

The purpose of the study was to analyse the frequency of sex-chromosome numerical abnormalities in human spermatozoa of infertile men by using a standardized experimental protocol of double target in-situ hybridization (ISH). The experiments were performed on decondensed sperm heads from 15 infertile patients (six cases of unexplained infertility and nine cases of severe oligoasthenoteratozoospermia). Three men of proven fertility were used as controls. The probes employed recognized the centromeric regions of human X chromosome and the long arm of the Y chromosome. In a smaller number of cases, additional experiments of double ISH were performed using centromeric probes for chromosomes 1 and 17. Signal detection was based on protocols of enzymatic cytochemical reactions. A total of 24,508, 24,679 and 42,285 cells were scored in the control, unexplained infertility and severe male factor groups of patients respectively. In all the patients in the ISH efficiency result was approximately 98%. In controls, unexplained infertility and severe male factor patients, the frequency of morphologically normal sperm cells carrying an abnormal chromosome constitution (XX or YY or XY or > 2 sex chromosomes signals) was 0.86, 0.75 and 1.35% respectively. The value of this last group of patients (severe male factor) was significantly higher than in the other two groups of patients (P < 0.008). The same findings were made using the autosomic probes. Our preliminary data support the possibility of an increased risk from paternal origin sex chromosome aneuploidies in children born after intracytoplasmic sperm injection (ICSI). Further investigations of the cytogenetic constitution of spermatozoa from severe male factor patients is warranted.

[Acute hyperparathyroidism associated with follicular carcinoma in the thyroid: possible role of juvenile cervical irradiation. Description of a case]. / Iperparatiroidismo acuto associato a carcinoma follicolare della tiroide: possibile ruolo dell'irradiazione cervicale giovanile. Descrizione di un caso clinico.

Acute onset of primary hyperparathyroidism is uncommon; neuropsychiatric signs are prominent clinical features in acute hypercalcemia and they can subside after normalization of serum calcium. Radiation therapy is a well-known risk factor for non medullary thyroid cancer, but it induces also parathyroid tumors. Data from the literature show that patients previously treated with neck radiation have an increased risk of primary hyperparathyroidism. Furthermore concomitant thyroid cancer is more frequent in radiation-induced hyperparathyroidism than in sporadic primary hyperparathyroidism. The case of a 63-year-old female patient who at the age of 14 had been irradiated to the neck for goiter and at the age of 50 had been repeatedly hospitalized for psychosis is presented. She was admitted to the hospital for suspected recurrence of psychosis, but clinical findings and urgent biochemical data showed on the contrary that she had a severe hypercalcemic crisis. Serum parathormone concentrations, neck echography and 99mTc-Sestamibi scintigraphy suggested hyperfunction of the right lower parathyroid gland; therefore the patient was operated on. Pathological examination disclosed a parathyroid adenoma but also two foci of follicular cancer in the right thyroid lobe with a metastasis to a lymph node were observed. Neuropsychiatric signs disappeared after normalization of calcemia and 6 months after operation the patient is free from psychiatric symptoms, despite she had stopped neurolectic drugs. It is underlined that patients who had received neck irradiation must be carefully observed because they are at increased risk of primary hyperparathyroidism and concurrent thyroid cancer.