Roentgeno-endovascular surgery of hypofunctional ovaries in varicosities of the ovarian veins]

Three degrees of ovarian varicocele in sterile women or women with menstrual disturbance were described on the basis of analysis of 62 superselective ovariophlebograms. A nonsurgical pathogenetic method for correction of ovarian hypofunction in disturbed circulation in the venous region of the pelvic organs was developed by cutting off the ovarian vein from the pathological renocaval vascular shunt with the help of roentgenovascular intervention. It is based upon transcatheter occlusion of the left ovarian vein and directly follows diagnostic phlebography. Roentgenoendovascular occlusion of the left ovarian vein was performed in 41 patients Ivanissevich's operation--in 8 patients. In 4-18 months after intervention, improved results of a clinical picture and functional diagnostic tests were observed in 46 patients. Of 19 women with passable uterine tubes 14 got pregnant.     

Magnetic resonance imaging (MRI) in the diagnosis of recurrences of ovarian cancer in the small pelvis

The paper provides the results of small pelvic magnetic resonance tomography (MRI) in 62 patients with ovarian cancer after primary special treatment. Out of them 50 patients were found to have recurrences and metastases of the underlying disease, 12 patients had clinical remission. The study yielded MR signs and MR semiotics of recurrences of ovarian cancer in the small pelvis. The capacities of MRI with low and high intensities of a magnetic field were comparatively studied in the diagnosis of recurrences and metastases of ovarian cancer.     

Factors affecting the response to the specific treatment of several forms of clinical anestrus in high producing dairy cows

This study was designed to examine estrous response rates to the therapeutic treatment of clinical anestrus in high producing dairy cows and to identify the factors that could affect these rates. Cows with silent ovulation (Subestrus group), cystic ovarian disease (Cyst group) or ovarian hypofunction (OH group) were given specific treatment for their disorder. Data were derived from 1764 treatments in cows producing a mean of 45.4 kg of milk upon treatment including: 889 subestrous cows, 367 cystic cows and 508 cows with ovarian hypofunction. Cows showing estrus following treatment exhibited a similar pregnancy rate to cows attaining natural estrus used as reference: 33% (337/1006) and 35% (626/1796), respectively. No significant differences in pregnancy rates were observed among the Subestrus, Cyst and OH groups (34% (196/571), 34% (44/130), 32% (97/305), respectively. Based on the odds ratio, an estrous response for all groups was less likely to occur in cows that had suffered previous anestrus, compared to cows that were anestrous for the first time, whereas the likelihood of an estrous response increased in cows treated after 90 days in milk. Our results indicate that previous anestrus and a late stage of lactation can have a negative and positive effect, respectively, on the estrous response to the specific treatment of clinical anestrus shown by high producing dairy cows. Treatment targeted at each type of clinical anestrus can render similar pregnancy rates to those shown by cows in natural estrus.     

Management of hyperandrogenism in adolescent girls.

Hyperandrogenism in adolescent girls can be a troubling problem because of the difficulty in establishing a diagnosis and in prescribing appropriate therapy. Androgen excess in adolescent patients encompasses a spectrum of clinical presentations, including acne, hirsutism, oligomenorrhea, amenorrhea, virilism, and ovarian cysts. Androgen excess is a clinical and chemical feature of idiopathic hirsutism, late-onset forms of congenital adrenal hyperplasia, and polycystic ovarian disease; in some cases, functional hyperandrogenism is discussed. We recommend screening for hyperandrogenism by measuring blood levels of testosterone, dehydroepiandrosterone sulfate, and delta 4-androstenedione, while others propose a first dexamethasone suppression test for evaluation of free testosterone, dehydroepiandrosterone sulfate, and cortisol. Treatment will be chosen according to particular symptoms such as acne, hirsutism, obesity, or oligomenorrhea.     

Platelet function in hypo- and hyperthyroidism

Alterations in cardiovascular hemodynamics are found in patients with hypofunction of the thyroid. Frank hypothyroidism favours the development of coronary heart disease. Platelets are thought to be important in atherosclerotic lesions initiation and progression. We studied platelet sensitivity to several agonists and to a physiological antagonist, prostacyclin, and thromboxane production in patients with hyperthyroidism and hypothyroidism. No statistically significant differences were found between platelets activities in patients and control subjects. We conclude that increased platelet function is not a direct indicator of susceptibility to cardiovascular diseases in patients with hypothyroidism whereas the hyperdynamic state, cardinal manifestation of thyrotoxicosis, is not associated with platelet activation.     

Ovarian development associated with first maturity in three Antarctic channichthyid species

It has been known for some time that yolk deposition and final ovarian maturation were prolonged processes for many Antarctic fish. The adolescent phase in three species of channichthyid has been studied, based on an extensive series of samples over five seasons. Samples were obtained during a series of abundance estimation surveys on the shelf around South Georgia. Fish were measured, and sex and maturity stage determined from macroscopic examination of the gonads. It was found that for female Champsocephalus gunnari and Pseudochaenichthys georgianus the adolescent phase lasts <1 year but in Chaenocephalus aceratus it lasts for nearly 4 years.     

Severe diabetic microangiopathy with normal glucose tolerance and pituitary infarction.

Blood glucose concentrations in a woman with severe retinopathy, nephropathy, and neuropathy were found to be within the normal range. A high random blood glucose concentration was recorded only once, six months before her initial presentation. At necropsy the anterior lobe of the pituitary gland showed old, extensive infarction. Occult pituitary hypofunction may explain severe diabetic microangiopathy in patients with normal glucose tolerance.     

Thyroid hypofunction in Down’s syndrome

Oxidative stress affecting the thyroxin biosynthesis might explain the proneness of patients with Down's syndrome (DS) (trisomia 21) to develop hypothyroidism. Thyroideal cells are exposed to endogenous H2O2 that acts as a cofactor for the iodination of thyroxin precursors. The gland has high levels of selenium-containing proteins, including peroxide-detoxicating enzyme proteins. The object of the present study was to explore the hypothesis of a role of an imbalance between toxic oxygen production and protective metalloenzymes during the development of thyroid hypofunction in DS patients. We analyzed serum levels of thyroid hormones and trace metals in 38 institutionalized adults with DS, using mentally retarded subjects matched for age, sex, and behavioral function as controls. The DS patients had significantly lower mean values of free thyroxin (fT4) and increased TSH (thyroid stimulating hormone), as compared to the controls. They had lower serum selenium than the controls. A positive correlation was observed between serum concentrations of fT4 and selenium in the DS patients (r = 0.393, p < 0.05). No significant differences were found between the fT4 or the TSH concentrations in the patients with and without circulating antithyroid autoantibodies. Our results support the suggestion that thyroid hypofunction in patients with Down's syndrome in some way is linked to the low serum levels of selenium found in these patients. It is suggested that selenium-containing proteins are involved in thyroid hormonal synthesis, by protecting biosynthetic processes against the toxicity of free oxygen radicals.     

The multifunctional protein glyceraldehyde-3-phosphate dehydrogenase is both regulated and controls colony-stimulating factor-1 messenger RNA stability in ovarian cancer

Although glyceraldehyde-3-phosphate dehydrogenase's (GAPDH) predilection for AU-rich elements has long been known, the expected connection between GAPDH and control of mRNA stability has never been made. Recently, we described GAPDH binding the AU-rich terminal 144 nt of the colony-stimulating factor-1 (CSF-1) 3' untranslated region (UTR), which we showed to be an mRNA decay element in ovarian cancer cells. CSF-1 is strongly correlated with the poor prognosis of patients with ovarian cancer. We investigated the functional significance of GAPDH's association with CSF-1 mRNA and found that GAPDH small interfering RNA reduces both CSF-1 mRNA and protein levels by destabilizing CSF-1 mRNA. CSF-1 mRNA half-lives were decreased by 50% in the presence of GAPDH small interfering RNA. RNA footprinting analysis of the 144 nt CSF-1 sequence revealed that GAPDH associates with a large AU-rich-containing region. The effects of binding of GAPDH protein or ovarian extracts to mutations of the AU-rich regions within the footprint were consistent with this finding. In a tissue array containing 256 ovarian and fallopian tube cancer specimens, we found that GAPDH was regulated in these cancers, with almost 50% of specimens having no GAPDH staining. Furthermore, we found that low GAPDH staining was associated with a low CSF-1 score (P = 0.008). In summary, GAPDH, a multifunctional protein, now adds regulation of mRNA stability to its repertoire. We are the first to evaluate the clinical role of GAPDH protein in cancer. In ovarian cancers, we show that GAPDH expression is regulated, and we now recognize that one of the many functions of GAPDH is to promote mRNA stability of CSF-1, an important cytokine in tumor progression.     

Three synchronous primary carcinomas in a patient with HNPCC associated with a novel germline mutation in MLH1: Case report

Background

Adnexal masses are not uncommon in patients with breast cancer. Breast cancer and ovarian malignancies are known to be associated. In patients with breast cancer and co-existing pleural effusions, ascites and adnexal masses, the probability of disseminated disease is high. Nevertheless, benign ovarian masses can mimic this clinical picture when they are associated with Meigs' syndrome making the work-up and management of these patients challenging. To our knowledge, there are no similar reports in the literature and therefore we present this case to highlight this entity.

Case presentation

A 56-year old woman presented with a 4 cm, grade 2, invasive ductal carcinoma of her left breast. Pre-treatment staging investigations showed a 13.5 cm mass in her left ovary, a small amount of ascites and a large right pleural effusion. Serum tumour markers showed a raised CA125 supporting the malignant nature of the ovarian mass. The cytology from the pleural effusion was indeterminate but thoracoscopic biopsy failed to show malignancy. The patient was strongly against mastectomy and she was commenced on neo-adjuvant Letrozole 2.5 mg daily with a view to perform breast conserving surgery. After a good response to the hormone manipulation, the patient had breast conserving surgery, axillary sampling and laparoscopic excision of the ovarian mass which was eventually found to be a benign ovarian fibroma.

Conclusion

Despite the high probability of disseminated malignancy when an ovarian mass associated with ascites if found in a patient with a breast cancer and pleural effusion, clinicians should be aware about rare benign syndromes, like Meigs', which may mimic a similar picture and mislead the diagnosis and management plan.     

Cyclic AMP-dependent protein kinase in mitochondria and cytosol from different-sized follicles and corpora lutea of porcine ovaries

cAMP-dependent protein kinase was examined in mitochondria and cytosol prepared from different-sized antral follicles and corpora lutea of porcine ovaries. In all ovarian tissues examined except small follicles, protein kinase-specific activity was significantly higher in mitochondria than in cytosol, with the highest to lowest activities being found in medium (4-6 mm) follicles, large (7-12 mm) follicles, corpora lutea, and small (1-3 mm) follicles, respectively. Using the photoaffinity analogue [32P]8-N3cAMP, two major cAMP binding proteins with Mr = 47,000 (the apparent regulatory subunit of protein kinase Type I) and 54,000-56,000 (Type II) were found in all ovarian preparations. Type II was predominant in the cytosol of all ovarian samples, with the cytosolic Type I to Type II ratio increasing from approximately 0.05 in small and medium follicles top approximately 0.20 in large follicles and corpora lutea. In contrast, ovarian mitochondrial preparations contained relatively more Type I than did cytosol, with the mitochondrial Type I to Type II ratio increasing from approximately 0.50 in small and medium follicles to 0.88 in large follicles and 2.96 in corpora lutea. Also, mitochondrial [4-14C]cholesterol conversion and 3 beta-hydroxysteroid dehydrogenase/isomerase activities increased with follicle size and luteinization. These results suggest that Type I may play a role in the regulation of ovarian mitochondrial steroidogenesis.     

Whole saliva and the diagnosis of Sjögren's Syndrome: an evaluation of patients who complain of dry mouth and dry eyes. Part 2: Immunologic findings

Sjögren's Syndrome (SS) is a multisystem, autoimmune disease characterised by generalised desiccation, exocrine hypofunction and serologic abnormalities. Last year we showed that the antibodies which are quasi-specific for diagnosis of SS, anti SS-A/Ro and anti SS-B/La, were present in the saliva of patients with this disease. Objective : To determine their presence in patients who complain of dry mouth and dry eyes. Setting: The study was conducted at the School of Dental Medicine, SUNY at Stony Brook. Patients : There were 49 patients (Mean Age= 54 ± 13 years). Tests : Serum was analysed for the SS and other antibodies with “Western Blot Autoantibody Strips”. Results: The findings showed that there was a strong correlation between the presence of the SS antibodies in the serum and the saliva. The SS antibodies were primarily found in the saliva of the patients whose resting and stimulated, whole saliva, flow rates were abnormally low. Antibodies to other autoimmune disease (Lupus, Seleroderma and Mixed Connective Tissue Disease) were also found in whole saliva. Conclusions : The findings in Part 1 of this study, of patients who had complained of dry mouth and dry eyes, suggest that those patients, who demonstrated low resting and stimulated flow rates and had lacrimal hypofunction, suffered from SS. The observation in this paper, that the whole saliva of these patients contains the SS antibodies, confirms this diagnosis. The data suggest that whole saliva can be used to establish the diagnosis of SS and other autoimmune diseases.     

Idiopathic premature ovarian failure in 63 young women

BACKGROUND: Premature ovarian failure (POF) in adolescents is defined as primary or secondary amenorrhea associated with high follicle-stimulating hormone (FSH) levels. In normal 46,XX patients, its etiology is most often unknown. We have evaluated the clinical, hormonal and ovarian phenotypes in patients with a normal karyotype who were diagnosed with POF before the age of 18. METHODS: Sixty-three patients were included in this retrospective study. RESULTS: The mean patient age was 20.4 years. The patients presented with three clinical patterns: lack of pubertal development (n = 23), primary amenorrhea with interrupted puberty (n = 18), and secondary amenorrhea with normal puberty (n = 22). Ten patients had a familial history of POF and 6 presented with hypothyroidism. The FSH, estradiol and inhibin B levels were not statistically different in the three clinical groups. Fifty percent of the patients presented small ovaries (length <2 cm) at ultrasonography. The presence of follicles was found at histology in only 7 of the 27 patients who underwent an ovarian biopsy. CONCLUSION: 46,XX patients presenting with early POF rarely presented a specific, identifiable disorder. We discuss the clinical management and different diagnosis strategies to improve our current knowledge of this syndrome.     

NEWS AND NOTES

In an investigation of relationships between ovarian function and thyroid function, three groups of ten women each were studied by means of radioactive iodine uptake. In the first group no significant changes were noted during normal menstrual cycles.The second group, women who had dysfunctional uterine bleeding and were under treatment with diethylstilbestrol, most of the patients had no significant change in the uptake of radioactive iodine. Three patients did show a small increase in the uptake. (A fourth patient had a very bizarre result with a very great increase in the uptake, but it is felt that some undetected error was involved.)The third group was made up of women without evident ovarian function. Under treatment with diethylstilbestrol one patient showed a small increase in iodine uptake. The other nine had no significant change.No convincing evidence was found of any change in thyroid function as measured by the uptake of radioactive iodine—either during normal menstrual cycles or following the administration of diethylstilbestrol in dosages of 3 mg. daily for two to three weeks.     

Relationship of ovarian and thyroid function

In an investigation of relationships between ovarian function and thyroid function, three groups of ten women each were studied by means of radioactive iodine uptake. In the first group no significant changes were noted during normal menstrual cycles. The second group, women who had dysfunctional uterine bleeding and were under treatment with diethylstilbestrol, most of the patients had no significant change in the uptake of radioactive iodine. Three patients did show a small increase in the uptake. (A fourth patient had a very bizarre result with a very great increase in the uptake, but it is felt that some undetected error was involved.)The third group was made up of women without evident ovarian function. Under treatment with diethylstilbestrol one patient showed a small increase in iodine uptake. The other nine had no significant change. No convincing evidence was found of any change in thyroid function as measured by the uptake of radioactive iodine-either during normal menstrual cycles or following the administration of diethylstilbestrol in dosages of 3 mg. daily for two to three weeks.     

The effectiveness of child and adolescent psychiatric treatments in a naturalistic outpatient setting

Data concerning the effectiveness of naturalistic treatments (treatment-as-usual) in child and adolescent psychiatric (CAP) services are scarce. The purpose of this prospective observational study was to examine the effectiveness of CAP treatments in a naturalistic outpatient setting. Three hundred six patients (attention-deficit/hyperactivity disorder, ADHD, n=94; conduct disorder, CD, n=57; anxiety disorder, AD, n=53; depressive disorder, DD, n=38; other diagnostic categories, n=64), from nine child and adolescent psychiatric practices in Germany, were evaluated. Treatment effects were compared between patients who received frequent treatment and patients who only participated in diagnostics and short interventions. Since randomization was not feasible, propensity score analysis methods were used. Regarding the total sample, no significant treatment effects were found. However, a subgroup analysis of the four most frequent disorders (ADHD, CD, AD, DD) showed small to moderate treatment effects in patients with ADHD and AD. In CD and DD subgroups, no significant treatment effects could be found. “Real-world” CAP outpatient treatment seems to produce significant effects for ADHD and AD, but not for CD and DD. Compared to efficacy studies, our results show that naturalistic treatment might be better than expected.     

Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer's disease

The prescribed drugs for treatment of cognitive deficits in Alzheimer's disease (AD) patients are regarded as symptomatic drugs. Effective disease modifying therapies are not yet prescribed in AD patients. Three major hallmarks of AD (e.g. cholinergic hypofunction, Aβ and tau neuropathologies) are closely linked raising the expectation that restoring the cholinergic hypofunction to normal, in particular via selective activation of M1 muscarinic receptors, may alter the onset or progression of AD dementia. This review is focused mainly on modulation of amyloid precursor processing and Aβ levels in the brain via cholinergic treatment strategies based on M1 muscarinic agonists versus other cholinergic treatments (e.g. cholinesterase inhibitors prescribed for treatment of AD, M2 antagonists and nicotinic agonists). Advantages and potential drawbacks of these treatment modalities are reviewed versus the notion that due to an elusive etiology of AD, future disease modifiers should address comprehensively most of these AD hallmarks (e.g. Aβ pathology, tau and tangle pathologies, as well as the cholinergic hypofunction and cognitive impairments). This major requirement may be fulfilled with M1-selective muscarinic agonists and less with other reviewed cholinergic treatments.     

Smad7 attenuates TGF-β-mediated aging-related hypofunction of submandibular glands

Submandibular glands have essential functions in taste, mastication, swallowing, and digestion. Submandibular gland hypofunction is prevalent in the elderly, impairing the patients’ quality of life. Current clinical treatment strategies have not decelerated or reversed the pathological process of submandibular gland hypofunction. Therefore, novel restoration strategies should be explored. However, studies on the mechanism of aging-related submandibular gland hypofunction remain very limited. The role of the TGF-β/Smad pathway in fibrosis has been studied in other organs. Therefore, this study aimed to elucidate the role of TGF-β/Smad signaling in the aging-related submandibular gland hypofunction. The results showed that Smad7 knockout in mice decreased the salivary flow rate. H&E, Masson trichrome, and immunohistochemistry staining of MCP-1 and α-SMA showed that Smad7 knockout in mice resulted in lymphocytic infiltration, acinar cell atrophy, and interstitial fibrosis. The Western blotting of collagen I and III also confirmed extensive fibrosis. We then found that Smad7 depletion resulted in the TGF-β-mediated fibrosis via mir-21, mir-29, and np_5318, and NFκB-driven inflammation activation. This study confirmed the inhibitory role of Smad7 in the aging-related submandibular gland hypofunction. Therefore, it provided a promising treatment target for aging-related dysfunction and sialadenitis of submandibular gland.     

Elevated Expression of the Serine-Arginine Protein Kinase 1 Gene in Ovarian Cancer and Its Role in Cisplatin Cytotoxicity In Vitro

Alternatively spliced variants of several oncogenes and tumor suppressors have been shown to be important for their tumorigenicity. In the present study we have tested whether serine-arginine protein kinase 1 (SRPK1), a major regulator of splicing factors, is involved in ovarian cancer progression and plays a role in chemo-sensitivity. By Western blot analyses, SRPK1 protein was found to be overexpressed in 4 out of 6 ovarian cancer cell lines as compared with an immortalized ovarian surface epithelial cell line; and in 55% of ovarian tumor samples as compared with non-neoplastic ovarian tissue samples. Reduction of SRPK1 expression using small interfering RNA (siRNA) encoding small hairpin RNA in ovarian cancer cells led to (i) reduced cell proliferation rate, slower cell cycle progression and compromised anchorage-independent growth and migration ability in vitro, (ii) decreased level of phosphorylation of multiple serine-arginine proteins, and P44/42MAPK and AKT proteins, and (iii) enhanced sensitivity to cisplatin. Together, these results suggest that elevated SRPK1 expression may play a role in ovarian tumorigenesis and SRPK1 may be a potential target for ovarian cancer therapy.