Spontaneous rupture of a hepatic cystadenoma and cystadenocarcinoma: report of two cases

Hepatobiliary cystadenomas and cystadenocarcinomas are rare tumors. Differentiating between these tumors and benign hepatic cysts may be difficult. Because of their rarity, diagnosis is often delayed and may result in inaccurate treatment, resulting in unnecessary morbidity and mortality. The purpose of this report is to draw attention to these entities and their complications. We report on two cases with spontaneous rupture of hepatobiliary cystadenoma and cystadenocarcinoma cysts, initially treated as simple hepatic cysts by aspiration, or by aspiration combined with sclerotherapy. The spontaneous rupture of the cysts appeared years after the initial treatment of the cysts, leading in one case to a prolonged stay in an intensive care unit. In both cases, a formal liver resection was carried out and microscopic investigations revealed a mucinous cystadenocarcinoma and cystadenoma. In conclusion, although hepatobiliary cystadenomas and cystadenocarcinomas are rare findings, they should not be forgotten in the diagnostic workshop when examining patients with hepatic cysts. If hepatobiliary cystadenomas and cystadenocarcinomas cannot be excluded following radiological imaging, surgery is recommended.     

Subcutaneous adipocytes from obese hyperinsulinemic women with polycystic ovary syndrome exhibit normal insulin sensitivity but reduced maximal insulin responsiveness

BACKGROUND: Polycystic ovary syndrome (PCOS) has a high prevalence in women and is often associated with insulin resistance and hence with aspects of the so-called metabolic syndrome. METHODS: Ten women diagnosed with PCOS were consecutively included (aged 21-39 years, average 30.2 +/- 1.9 years; body mass index 28.4-42.5 kg/m2, average 37.5 +/- 1.7 kg/m2 (mean +/- s.e.)). Adipocytes were isolated from the subcutaneous fat and, after overnight incubation to recover from insulin resistance due to the surgical cell isolation procedures, they were analyzed for insulin sensitivity. RESULTS: The patients with PCOS exhibited marked clinical hyperinsulinemia with 3.6-fold higher blood levels of C-peptide than a healthy lean control group (1.7 +/- 0.2 and 0.5 +/- 0.02 nmol/l respectively, P < 0.0001). The patients with PCOS also exhibited 2.4-fold higher concentrations of serum triacylglycerol (2.1 +/- 0.3 and 0.9 +/- 0.06 mmol/l respectively, P < 0.0001), but only slightly elevated blood pressure (118 +/- 12/76 +/- 6 and 113 +/- 7/72 +/- 6 mmHg respectively, P = 0.055/0.046). However, insulin sensitivity for stimulation of glucose transport in the isolated adipocytes was indistinguishable from a non-PCOS, non-diabetic control group, while the maximal insulin effect on glucose uptake was significantly lower (2.2 +/- 0.2- and 3.8 +/- 0.8-fold respectively, P = 0.02). CONCLUSIONS: Subcutaneous adipocytes from patients with PCOS do not display reduced insulin sensitivity. The findings show that the insulin resistance of PCOS is qualitatively different from that of type 2 diabetes.     

Relationship between allopregnanolone and negative mood in postmenopausal women taking sequential hormone replacement therapy with vaginal progesterone

OBJECTIVE: To compare severity of negative mood and physical symptoms between women with different progesterone, allopregnanolone, and pregnanolone plasma concentrations during sequential Hormone Replacement Therapy (HRT) with vaginal progesterone suppositories. DESIGN: A randomized, placebo-controlled, double-blind, crossover study. METHOD: Postmenopausal women (n=36) with climacteric symptoms were treated with 2mg estradiol daily during three 28-day cycles. Vaginal progesterone suppositories with 400, 800 mg/day or placebo were added sequentially for 14 days per cycle. Daily symptom ratings using a validated rating scale were kept. Blood samples for progesterone, allopregnanolone, and pregnanolone radioimmunoassays were collected during each treatment cycle. RESULTS: Women were divided into three groups (low, medium, and high) based on plasma allopregnanolone concentration during progesterone treatment. The concentration of allopregnanolone in the medium group corresponds to the concentration seen during the mid luteal phase of the menstrual cycle. Within women with medium allopregnanolone concentration significantly more negative mood and physical symptoms were rated during progesterone treatment compared to treatment with unopposed estrogen or placebo. Between women significantly more negative mood symptoms were seen during progesterone treatment cycles with medium allopregnanolone concentration compared to cycles with low concentration. Plasma progesterone, allopregnanolone, and pregnanolone concentrations increased with increasing progesterone dose. Progesterone and allopregnanolone plasma concentrations increased 2h after vaginal administration of progesterone at 400 and 800 mg/day. CONCLUSION: Vaginal progesterone in sequential HRT causes negative mood, most likely mediated via allopregnanolone.     

Reduced full-field electroretinogram (ERG) in a patient treated with methotrexate

PURPOSE: To examine retinal function in a patient with decreased vision possibly due to treatment with methotrexate. METHODS: Ophthalmological examination included testing of visual acuity (VA), fundus inspection, fundus photography, and kinetic perimetry. Retinal function was tested objectively with three electrophysiological methods: full-field electroretinography (ERG), multifocal electroretinography (mfERg) and also electro-oculography (EOG). RESULTS: A 13-year-old boy with psoriasis arthritis had been treated with methotrexate on a weekly basis for 8.5 years. After terminating treatment, his VA, which was reduced to 0.3 in both eyes initially, improved during the following 3 years but did not return to normal. No visual field defects were found with kinetic perimetry. The rod and cone responses in the full-field ERG were markedly reduced in b-wave amplitude initially, but grew slowly to nearly normal values 3 years later. After withdrawal of the drug, the mfERG demonstrated normal responses in the macular region. The Arden index in the EOG was normal. CONCLUSION: Chronic treatment with methotrexate may affect VA, and mat reversible reduce rod and cone function. In patients who use systemic medication and who vision is reduced, objective evaluation of retinal function with electrophysiological methods is recommended.     

Full-field ERG, multifocal ERG and multifocal VEP in patients with retinitis pigmentosa and residual central visual fields

PURPOSE: To evaluate (with three different electrophysiological methods) the residual retinal function in a selected group of patients with retinitis pigmentosa and remaining small central visual fields. METHODS: Fourteen patients from several different genetic subgroups, who had been followed with visual acuity and visual field testing for periods up to 32 years, were examined. Ophthalmological examination included full-field electroretinography (ERG), multifocal electroretinography (mfERG) and multifocal visual evoked potential (mfVEP). RESULTS: The ERGs were severely reduced in all patients. The mfERGs demonstrated the residual central retinal function in five of the patients. The mfVEPs showed measurable amplitudes centrally in most of the patients. The follow-up examinations demonstrated the slowly progressive course of the disease with preservation or only slight further loss of visual fields over a period of 7-32 years. CONCLUSION: Patients with retinitis pigmentosa may not always follow the typical natural course with progressive loss of visual fields, which may in some patients remain unaffected over several decades. Multifocal ERG and mfVEP may be clinically useful for evaluating remaining visual function in these patients.     

Design and synthesis of potent inhibitors of the malaria aspartyl proteases plasmepsin I and II. Use of solid-phase synthesis to explore novel statine motifs

Picomolar to low nanomolar inhibitors of the two aspartic proteases plasmepsin (Plm) I and II, from the malaria parasite Plasmodium falciparum, have been identified from sets of libraries containing novel statine-like templates modified at the amino and carboxy terminus. The syntheses of the novel statine templates were carried out in solution phase using efficient synthetic routes and resulting in excellent stereochemical control. The most promising statine template was attached to solid support and diversified by use of parallel synthesis. The products were evaluated for their Plm I and II inhibitory activity as well as their selectivity over cathepsin D. Selected inhibitors were, in addition, evaluated for their inhibition of parasite growth in cultured infected human red blood cells. The most potent inhibitor in this report, compound 16, displays Ki values of 0.5 and 2.2 nM for Plm I and II, respectively. Inhibitor 16 is also effective in attenuating parasite growth in red blood cells showing 51% inhibition at a concentration of 5 microM. Several inhibitors have been identified that exhibit Ki values between 0.5 and 74 nM for both Plm I and II. Some of these inhibitors also show excellent selectivity vs cathepsin D.     

Loss of neural cell adhesion molecule induces tumor metastasis by up-regulating lymphangiogenesis

Reduced expression of neural cell adhesion molecule (NCAM) has been implicated in the progression to tumor malignancy in cancer patients. Previously, we have shown that the loss of NCAM function causes the formation of lymph node metastasis in a transgenic mouse model of pancreatic beta cell carcinogenesis (Rip1Tag2). Here we show that tumors of NCAM-deficient Rip1Tag2 transgenic mice exhibit up-regulated expression of the lymphangiogenic factors vascular endothelial growth factor (VEGF)-C and -D (17% in wild-type versus 60% in NCAM-deficient Rip1Tag2 mice) and, with it, increased lymphangiogenesis (0% in wild-type versus 19% in NCAM-deficient Rip1Tag2 mice). Repression of VEGF-C and -D function by adenoviral expression of a soluble form of their cognate receptor, VEGF receptor-3, results in reduced tumor lymphangiogenesis (56% versus 28% in control versus treated mice) and lymph node metastasis (36% versus 8% in control versus treated mice). The results indicate that the loss of NCAM function causes lymph node metastasis via VEGF-C- and VEGF-D-mediated lymphangiogenesis. These results also establish Rip1Tag2;NCAM-deficient mice as a unique model for stochastic, endogenous tumor lymphangiogenesis and lymph node metastasis in immunocompetent mice.     

Alterations in electroretinograms and retinal morphology in rabbits treated with vigabatrin

PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina. METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration. Full-field electroretinograms demonstrated normal rod function in all treated rabbits, but reduced cone function in two of the five treated rabbits verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery in all five treated rabbits, one of which had staining also in the centrally localized glial cells. The treated rabbits also demonstrated a weaker GAD staining in the IPL and less positive amacrine cells, compared to the controls. Only two treated rabbits had normal GABA staining while three had an enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three out of five treated rabbits the Müller cells were short, stubby and fragmented, with swollen endfeet. CONCLUSION: This study demonstrates changes in histopathology caused by vigabatrin in an animal model, which has not been reported previously. We have found that vigabatrin orally administrated to rabbits does not affect rod function but may reduce cone function in the full-field electroretinogram, which is similar to the previously reported vigabatrin effect on the human ERG. The results indicate that vigabatrin may damage or influence, at least one cell type in the rabbit retina.     

Functional outcome,rehabilitation use and length of hospital stay for stroke patients in south Madrid

BACKGROUND: Health status and use of resources by stroke patients in Spain are unknown. METHODS: A total of 103 acute stroke patients resident in south Madrid, population 665,168, were seen in 1996 at a general hospital and three primary care centres and evaluated at 5-10 days, 3 and 6 months after stroke. Health outcomes and patterns of rehabilitation and hospital use by patient groups were studied using multivariate logistic regression. RESULTS: The group receiving rehabilitation exhibited higher levels of impairment, disability and handicap at each time point, these differences decreasing with time, except in the distribution of walking ability which was unimodal in that group. Younger age, poor walking ability and motor capacity, pain on the paretic side and living with a spouse predicted use of rehabilitation; low level of education predicted a long hospital stay. CONCLUSION: Rehabilitation for stroke in south Madrid was sparse and used mainly by young, severely affected patients.