High levels of serum allopregnanolone in women with premature ovarian failure

BACKGROUND: Blue-on-yellow (B/Y) perimetry can reveal visual field defects earlier and larger in extent than white-on-white (W/W) perimetry. The Heidelberg Retina Tomograph (HRT) produces a three-dimensional image of the optic disc. The aim of this study was to compare the strength of the association of the B/Y and W/W visual hemifield mean deviation (HMD) variables with the optic nerve head (ONH) morphological variables of the respective area. METHODS: We evaluated one randomly chosen eye of 40 normal subjects and 37 patients with ocular hypertension and different stages of glaucoma. The B/Y and W/W visual fields (program 30-2) were obtained with a Humphrey perimeter. Results of both visual fields were adjusted for the patient's age and lens transmission index measured with a lens fluorometer. HMD was calculated as the difference between the measured and expected hemifield mean sensitivity values, predicted by the regression model fitted in our nonglaucomatous subject data. The HRT with the software version 1.11 was used to acquire and evaluate the topographic measurements of the optic disc. RESULTS: The B/Y and W/W visual field HMDs showed statistically significant correlation with ONH parameters such as cup shape measure (CSM), rim volume, rim area, mean retinal nerve fiber layer (RNFL) thickness and RNFL cross-sectional area. With forward stepwise logistic regression analysis using B/Y hemifield data 38% of the glaucoma patient's normal W/W hemifields were classified abnormal. With the CSM alone in the model 52% of the cases were classified abnormal. CONCLUSIONS: B/Y visual field hemifield mean deviation values correlate well with ONH parameters examined with the HRT.     

Seven new cases of Cayler cardiofacial syndrome with chromosome 22q11.2 deletion, including a familial case

Pulmonary lymphangitic carcinomatosis (PLC) is an unusual presentation of diffuse infiltrative lung disease. In this report we present two cases secondary to breast cancer; the diagnosis was made by means of transbronchial lung biopsy or postmortem examination. The goal of this study was to analyze the scintigraphic pattern of pulmonary perfusion performed with technetium-99m macroaggregated albumin (99mTc-MAA) in the hope of achieving improved recognition of PLC and its subsequent diagnosis. Upon admission, both patients underwent routine clinical exams followed by chest X-rays. The second patient also underwent CT examination, and both were ultimately examined using pulmonary perfusion scintigraphy with 99mTc-MAA. In the various exams performed, the most reliable and easily identified diagnostic finding turned out to be a characteristic 'fragmented' lung pattern revealed with the perfusion lung scan. Unfortunately, in both cases the patients' conditions rapidly worsened and death occurred shortly following scintigraphy. We were able to conclude that the recognition of the mentioned fragmented scintigraphic lung pattern may be useful in suspected PLC, whereas the nonspecific clinical presentation of this pathology makes diagnosis extremely difficult, with the most significant results being achieved through a comparison of scintigraphic and high resolution CT data.     

Inheritance in idiopathic premature ovarian failure: analysis of 71 cases

Premature ovarian failure is defined as cessation of ovarian function under the age of 40 years and affects approximately 1% of women in the general population. The aetiology of this disorder is still unknown in most cases. Although there have been some reports of familial premature ovarian failure, very little is known about the incidence and inheritance pattern of its idiopathic form. The aims of this study were to investigate the incidence and inheritance pattern of familial premature ovarian failure in a homogeneous group of patients with premature idiopathic menopause and to identify possible clinical differences between patients with the familial and the sporadic form of premature ovarian failure. A total of 71 women were recruited into the study. Clinical assessments and genetic counselling showed that 22 (31%) patients had familial premature ovarian failure, this high incidence strongly suggesting that the disorder is a recognizable heritable entity. There was a statistically significant (P < 0.05) difference in the median age of precocious menopause in patients with sporadic and familial premature ovarian failure (31.0 and 37.5 years of age in the two groups, respectively). Pedigree analysis strongly suggests the existence of a familial pattern of premature ovarian failure with a dominant maternal and/or paternal transmission and incomplete penetrance. In the presence of familial history of premature ovarian failure, reproductive counselling is recommended.     

New advances in the treatment of infertility in women with ovarian failure

Ovarian failure is heterogeneous in etiology and may occur at various points in a woman's life. As such, it may interfere with fertility. Clinical presentation ranges from complete cessation of menses to oligomenorrhea to the continuation of menses with elevated gonadotropins. Various therapies have been used in an attempt to induce fertility, including sex steroids and gonadotropin-releasing hormone agonists to suppress circulating gonadotropin alone or in combination with estrogen or gonadotropin-releasing hormone agonists to induce ovulation. Corticosteroids are also used to overcome autoimmunity. Randomized therapeutic trials are rare and fail to demonstrate any significant improvement in ovulation and pregnancy rates. Donor oocytes have demonstrated high success rates and have proven to be useful in patients with both premature ovarian failure and natural menopause. Pregnancies have been initiated and maintained in women through 60 years of age. Thus, for those accepting of the technique, oocyte donation appears to be the treatment of choice for hypergonadotropic hypogonadism.     

A molecular cytogenetic analysis of X chromosome repatterning in the Bovidae: transpositions, inversions, and phylogenetic inference

Chromosomal homologies among the X chromosomes of species representative of eight bovid subfamilies and most of the recognized tribes were established using a combination of FISH and conventional G- and C-banding. Our analyses allowed for the delimitation of three X chromosome types represented, respectively, by cattle (Bovinae, tribe Bovini), the tragelaphines (Bovinae, tribe Tragelaphini), and a large assemblage comprising all the remaining subfamilies and their tribes (the Cephalophinae, Hippotraginae, Alcelaphinae, Antilopinae, Aepycerotinae, Peleinae, and Caprinae). The use of the bacterial artificial chromosome probe BAC 101 (which maps to Xp12 in cattle) and an Xp painting probe comprising sequences specific for the short arm of cattle Xp (Xp24-->p12) allowed us to orient this region, which has moved as a conserved euchromatic block during the evolution of the bovid X chromosome. We show that the differences between the three chromosomal types are attributable to a transposition, two inversions, and heterochromatic additions/deletions. A paucity of comparative mapping data precludes the assignment of the sequences contained in cattle Xp to either the presumed conserved (XCR) or the recently added (XAR) region of the eutherian X chromosome, and the reasons for the retention of these sequences as an evolutionarily conserved unit in the intrachromosomal restructuring of the bovid X across lineages remain enigmatic.     

A case of de novo interstitial deletion of chromosome 5(q33q34)

Regional intrahepatic chemotherapy of inoperable primary and secondary liver tumours can achieve, as compared with the little effective systemic chemotherapy, a higher percentage of therapeutic responses. The objective of regional chemoimmunotherapy, i.e. the use of cytokines, in particular interferon alpha (IFN-a) and interleukin-2 (IL-2) in the therapeutic regimens is to improve the survival of patients with malignant liver tumours. One of the main prerequisites of the effect of locally administered cytokines is activation of hepatic lymphocytes (LAL)-liver associated lymphocytes, effectors with specific phenotype and potential anti-tumourous effect directly in the target area. Although in regional monotherapy the effectiveness of cytokines is low, regimens combining the administration of cytostatics with IL-2 achieve a 50-70% therapeutic response. The authors summarize basic data on the regional administration of cytokines and present an review of combined regimens of regional chemoimmunotherapy, including their own protocol of the Masaryk Oncological Institute in Brno.     

High frequency of chromosome 9 deletion in ovarian cancer: evidence for three tumour-suppressor loci

India has one of the world's highest incidences of oral cancer. It is believed that the widespread habit of betel quid chewing is an important risk factor as it exposes the oral mucosa to known carcinogens. It also induces physical abrasions, which may create mitogenic environments during wound healing as gateways for infections. A recent study from our laboratories identified human papillomavirus (HPV) DNA, mostly of the high-risk types HPV-16 and HPV-18, in 67 of 91 oral cancer lesions from a cohort of Indian patients consisting mostly of betel quid users. This suggested a viral etiology of some lesions but tumorigenesis in the absence of viruses in other lesions. Here, we examined whether the p53 gene, whose function is abrogated by the product of the HPV gene E6, would be mutated in those oral cancers that were free of HPV DNA, and we found point mutations at known hot spots for mutational alteration of p53 in 4 of 23 lesions. We also considered the possibility that p21, a target of regulation by the p53 protein, may be mutationally altered in tumors with a functional p53 gene. While we did not identify mutations in the p21 gene, 6 of 11 lesions contained a polymorphism that may be associated with cancer. Interestingly, 3 of 23 lesions had mutations in the p16 gene, a third regulator of the cell cycle which is frequently mutated in melanoma but rarely in other cancers, with 1 lesion even having a mutation in the p53 as well as in the p16 gene. Our data point to p53 and p16 as gene targets of oral carcinogenesis, with chemicals in the betel quid possibly functioning in these tumors as carcinogens.     

A case of familial ventricular tachycardia

From January 1986 to December 1989, 157 previously untreated patients, with Hodgkin's disease stage I or II without bulky disease, were enrolled in a clinical comparative study. The objectives of the study were to compare the efficacy and safety of using epirubicine or mitoxantrone instead of adriamycin in the combination chemotherapy regimen ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine). The complete response rate was better in the patients treated with the ABVD or EBVD regimens compared to the MBVD arm. Also, differences in overall survival and relapse-free survival were better in the patients who received ABVD or EBVD compared to the MBVD regimen. Hematological, gastrointestinal and cardiac toxicity were similar in the three groups. Dose intensity, delays and complications were also similar in the three groups. The mitoxantrone-containing regimen was found to have less efficacy in comparison to the other regimens tested in the present study in patients with favorable stage I or II Hodgkin's disease.     

Triplet pregnancy in premature ovarian failure after oocyte donation and in vitro fertilization: a case report and review of literature

Oocyte donation in premature ovarian failure patients has become an extended indication for In Vitro Fertilization (IVF) procedure. Here the first case report is presented in Taiwan, R.O.C. of a triplet pregnancy in a patient with premature ovarian failure. After an adequate hormonal replacement therapy with oral premarin and intramuscular progesterone for endometrium preparation, the transfer on D15 of four embryos (with donated oocytes and IVF) resulted in implantation of three. Pregnancy support was provided also by oral premarin and intramuscular progesterone until the tenth week of gestational age (GA). The patient received Caesarean section at 35 weeks GA with delivery of three healthy babies weighing 2530 gm, 2420 gm, and 1810 gm respectively on Aug. 17, 1990.     

A familial case of hyper-IgM immunodeficiency

A 22-year-old male was diagnosed as having immunodeficiency with hyper-IgM based upon recurrent pneumonia, marked elevation of serum IgM and markedly decreased level of IgG. IgG-or IgA-bearing B cells were not detected in peripheral blood while a number and a proportion of peripheral blood T lymphocytes were normal. Peripheral blood lymphocytes from this patient proliferated normally in response to T-independent and T-dependent B cell mitogens, and to T cell mitogens. Furthermore, the same type of dysgammaglobulinemia with increased IgM was found in the patient's father and brother. From these observations, it is suggested that it is a rare case of autosomal dominant or polygenal inheritance of hyper-IgM immunodeficiency.     

A familial case with generalized resistance to thyroid hormones

BACKGROUND: The syndrome of generalized resistance to thyroid hormones is more frequent than was thought. CASE REPORTS: A 13-year old girl was examined for her short stature. Evaluation of her thyroid function showed increased levels of IT3 and IT4 and normal value of TSH; she also had mosaic Turner's syndrome. Her cousin was rapidly diagnosed as suffering from the same syndrome because of moderately high thyrotropic levels found during neonatal screening; this syndrome was confirmed by molecular biology tests. Five generations of this family were identified as being affected with a pattern indicating autosomal dominant inheritance. CONCLUSION: The clinical manifestations of familial generalized resistance to thyroid hormones vary but this syndrome is easy to biologically confirm. The importance of diagnosing affected children as early as possible should be emphasized, as in such cases their development must be closely monitored particularly where their growth and neurodevelopment are concerned.     

Partial deletion of chromosome 6p: autopsy findings in a premature infant and review of the literature

Autopsy findings for a premature infant with terminal deletion of 6p [46, XY, del(6)p23] are reported. The infant had multiple dysmorphic features, cleft lip and palate, abnormal external genitalia, diverticulum of right ventricle, and hydrocephalus with cerebellar hypoplasia, with absent corpus callosum and cerebellar vermis.     

A case of syndrome X

Type 2 diabetes is increasing in prevalence and is predominantly managed in general practice. This series contains case histories which deal with some of the metabolic problems that may be encountered in the management of these patients and indicates some of the many issues, other than glycaemic control, that need to be considered.     

A review on family history of breast cancer: screening and counseling proposals for women with familial (non-hereditary) breast cancer

In a neural model of olfactory bulb processing, we demonstrate the putative role of the modulation of two types of inhibition, inspired by electrophysiological data on the effect of acetylcholine and noradrenaline on olfactory bulb synaptic transmission. Feedback regulation of modulation based on bulbar activity serves to 'normalize' the activity of output neurons in response to different levels of input activities. This mechanism also decreases the overlap between pairs of output patterns (Mitral cell activities), enhancing the discrimination between overlapping olfactory input patterns. The effect of the modulation at the two levels of interneurons is complementary: while an increase in periglomerular inhibition decreases the number of responding output neurons, a decrease in granule cell inhibition increases the firing frequencies of these neurons.     

A de novo interstitial deletion of chromosome 15 band q25 as revealed by FISH-technique

We report a new chromosomal finding in a 20 month-old girl. The minor clinical features included: moderate mental retardation, microcephaly, mild hypotonia and hypertelorism. Initially, what appeared to be a terminal deletion of the long arm of one chromosome 15 [15q26-->qter] was determined to be an interstitial deletion involving band 15q25 as revealed by FISH-technique, showing the presence of intact telomeric hybridization signals. The cytogenetic diagnosis was thus modified to 46,XX, del (15) (pter-->q24::q26--> qter). Nevertheless, the function of the enzyme telomerase should not be ignored, as healing could occur following such terminal deletions. Consequently, it will remain a difficult task to distinguish terminal deletions from those that are interstitial.     

Identification of the chromosome 14 origin of a C-negative marker associated with a 14q32 deletion by chromosome painting

A constitutional chromosome 14 rearrangement was observed in a female with a psychodevelopmental disorder. Karyotype analysis using a variety of chromosome techniques, QFQ, GTG, CBG, Ag-NOR and DA-DAPI, showed a deletion of chromosome 14q32.1-qter region in association with a supernumerary marker chromosome. The marker, resembling a submetacentric, approximately half the size of a G group chromosome is C band and Ag-NOR negative. The heteromorphism of the satellites showed that the deleted chromosome 14 is paternal in origin. Chromosome painting using an Alu-PCR probe specific for the human chromosome 14 and fluorescent in situ hybridization (FISH) showed that the marker contains chromosome 14q32 sequences. It is likely that the marker was generated from the deleted chromosome 14 region through a complex rearrangement.