Appendiceal Mucocele – Unexpected Diagnosis in a Gynecology Department

Appendiceal mucocele is a rare entity, occuring in < 1% among appendicectomies, with a female predominance 4/1 (F/M) and a mean age of more than 50 years. The preoperative diagnosis is difficult; in most cases, it´s an intraoperative finding. In such work, we describe the two clinical cases occurring in last 10 years in our Department. Case 1 - 56 years old, posmenopausal, referred to our Department (02/2004) because an asymptomatic right adnexal septated cystic image, 53x48mm, with hipovascularized septa and a vascularised capsule with low flow resistance (IR 0,57). CA 125 elevated (71,3 U/mL).Exploratory laparotomy: an ovary increased, with a gelatanious consistency and an appendicular enlargement. Extemporaneous examination: a pseudomixoma peritonei, associated with a mucinous appendicular and an ovary tumor. It was performed a radical surgery. The histo-pathological analysis showed a mucinous cystadenoma of the appendix with peritoneal mucinous dissemination involving the ovary. Expectant attitude since the surgery, without clinical and imaging signs of recurrence. Case 2- 62 years old posmenopausal and asymptomatic woman, with a large adnexal mass detected on routine pelvic ultrasound: heterogeneous, 94x84mm without vascularisation signs in its interior. CEA was elevated (41,47U/ml). Exploratory laparotomy (02/2010): enlarged appendix and macroscopically normal pelvic organs. An appendicectomy was performed. The histo-pathological analysis showed a 10cm mucinous cystadenoma of the appendix and signs of localized (visceral peritoneal surface) pseudomyxoma peritonei. Currently she’s clinically well, in an expectant attitude. Despite mucoceles of the appendix are rare, they should be considered in women presenting with abnormal quadrant masses.

USE OF LOPINAVIR/RITONAVIR ASSOCIATED WITH ERGOTAMINE RESULTING IN FOOT AMPUTATION: BRIEF COMMUNICATION

A 32-year-old female, was diagnosed in 2004 with a C1 HIV1 infection, using zidovudine/lamivudine 300/150 mg BID and lopinavir/ritonavir 400/100 mg BID, in addition to prophylaxis with trimethoprim-sulfamethoxazole 800/160 mg QD, but no prophylaxis with macrolide antibiotics. The patient presented with a severe headache and was prescribed two capsules of the anti-migraine drug Ormigrein™, which contained ergotamine tartrate 1 mg, caffeine 100 mg, paracetamol 220 mg, hyoscyamine sulfate 87.5 mcg, and atropine sulfate 12.5 mcg. Afterwards she was prescribed one capsule of Ormigrein every 30 minutes for a total of six capsules a day. The patient took the medication as prescribed but developed a pain in her left ankle three days later, which evolved to the need for amputation.

Understanding the relationship between central metabolism and virulence in the human pathogen Streptococcus pneumoniae

Dissertation presented to obtain the Ph.D. degree in Biochemistry

EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS

Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity) and eggs hatchability (fertility) in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors.

IgG4-Related Hashimoto's Thyroiditis - A New Variant of a Well Known Disease

Hashimoto's thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment.

Macrofilaricidal effects of chloroquine on adult Onchocerca volvulus by local infiltration of palpable onchocercal nodules

The macrofilaricidal effects of local infiltration of high concentrations of chloroquine into the capsule of onchocercal nodules on adult worms of Onchocerca volvulus was determined. Six weeks post infiltration, histological examination of single nodules showed all adult worms to be dead. With nodule conglomerates, there was localized action of chloroquine only on the adult worms in the infiltrated nodule, with no diffusion of the drug to adjacent nodules. Chloroquine infiltration of young, recently formed nodules to reduce the adult worm load of infected individuals may be an alternative method to costly nodulectomy.

Studies of the assembly of the Streptococcus pneumoniae capsular polysaccharide

Dissertation presented to obtain the Ph.D degree in Biology.

Larvicidal activity of oil-resin fractions from the Brazilian medicinal plant Copaifera reticulata Ducke (Leguminosae-Caesalpinoideae) against Aedes aegypti (Diptera, Culicidae)

Oil-resin fractions from Copaifera reticulata Ducke (Leguminosae-Caesalpinoideae) were evaluated for larvicidal activity on third larval instars of Aedes aegypti, in searching for alternative control methods for this mosquito. The bioactive fractions were chemically monitored by thin-layer chromatography, ¹H and 13C nuclear magnetic resonance and mass spectrometry. Bioassays were performed using five repetitions, at a temperature of 28 ± 1°C, relative humidity of 80 ± 5% and light and dark cycles of 12h. Mortality was indicated by darkening of the cephalic capsule after 24h of exposure of the larvae to the solutions. The most active fractions were CRM1-4 (sesquiterpenes) and CRM5-7 (labdane diterpenes), which showed LC50 values of 0.2 and 0.8ppm, respectively.

Soap bubble appearance in brain magnetic resonance imaging: cryptococcal meningoencephalitis

Although cryptococcal infections begin in the lungs, meningoencephalitis is the most frequently encountered manifestation of cryptococcosis among individuals with advanced immunosuppression. As the infection progresses along the Virchow-Robin spaces, these structures may become dilated with mucoid material produced by the capsule of the organism. We report a case of a 24-year-old man with cryptococcal meningoencephalitis in which magnetic resonance imaging showed clusters of gelatinous pseudocysts in the periventricular white matter, basal ganglia, mammillary bodies, midbrain peduncles and nucleus dentatus with a soap bubble appearance.

Dirofilariasis involving the oral cavity: report of the first case from South America

Oral dirofilariasis is very rare with non-specific clinical manifestations. Here, we report the case of a 65-year-old South American woman with a submucosal nodule on her right buccal mucosa. The nodule was slightly tender and painful. Differential diagnoses included mesenchymal (lipoma or fibrolipoma, solitary fibrous tumor, and neurofibroma) or glandular benign tumors (pleomorphic adenoma) with secondary infections. We performed excisional biopsy. A histopathological examination revealed a dense fibrous capsule and a single female filarial worm showing double uterus appearance, neural plaque, well-developed musculature and intestinal apparatus. Dirofilariasis was diagnosed, and the patient was followed-up for 12 months without recurrence.

Biomimetic mineralization: encapsulation in calcium carbonate shells

Calcium carbonate biomineralization is a self-assembly process that has been studied to be applied in the biomedical field to encapsulate biomolecules. Advantages of engineering mineral capsules include improved drug loading efficiencies and protection against external environment. However, common production methods result in heterogeneous capsules and subject biomolecules to heat and vibration which cause irreversible damage. To overcome these issues, a microfluidic device was designed, manufactured and tested in terms of selectivity for water and oil to produce a W/O/W emulsion. During the development of this work there was one critical challenge: the selective functionalization in closed microfluidic channels. Wet chemical oxidation of PDMS with 1M NaOH, confirmed by FTIR, followed by adsorption of polyelectrolytes - PDADMAC/PSS - confirmed by UV-Vis and AFM results, render the surface of PDMS hydrophilic. UV-Vis spectroscopy also confirmed that this modification did not affect PDMS optical properties, making possible to monitor fluids and droplets. More important, with this approach PDMS remains hydrophilic over time. However, due to equipment constrains selectivity in microchannels was not achieved. Therefore, emulsion studies took place with conventional methods. Several systems were tried, with promising results achieved with CaCO3 in-situ precipitation, without the use of polymers or magnesium. This mineral stabilizes oil droplets in water, but not in air due to incomplete capsule formation.

Enteroscopia por cápsula e doença de Crohn: Caminhos para a otimização

Tese de Doutoramento em Medicina

Engineering modular viral scaffolds for targeted bacterial population editing

Bacteria are central to human health and disease, but existing tools to edit microbial consortia are limited. For example, broad-spectrum antibiotics are unable to precisely manipulate bacterial communities. Bacteriophages can provide highly specific targeting of bacteria, but assembling well-defined phage cocktails solely with natural phages can be a time-, labor- and cost-intensive process. Here, we present a synthetic biology strategy to modulate phage host ranges by engineering phage genomes in Saccharomyces cerevisiae. We used this technology to redirect Escherichia coli phage scaffolds to target pathogenic Yersinia and Klebsiella bacteria, and conversely, Klebsiella phage scaffolds to target E. coli by modular swapping of phage tail components. The synthetic phages achieved efficient killing of their new target bacteria and were used to selectively remove bacteria from multi-species bacterial communities with cocktails based on common viral scaffolds. We envision this approach accelerating phage biology studies and enabling new technologies for bacterial population editing.

Improving diagnostic yield in obscure gastrointestinal bleeding - how virtual chromoendoscopy may be the answer

Background and aim: A significant proportion of patients presenting with obscure gastrointestinal bleeding (OGIB) have negative small bowel capsule endoscopy (SBCE) examinations, and yet remain at risk of rebleeding. We aimed to evaluate whether a second-look review of SBCE images using flexible spectral color enhancement (FICE) may improve the detection of potentially bleeding lesions. Materials and methods: This was a retrospective, single-center study including consecutive patients with OGIB subjected to SBCE, whose standard white light examination was nondiagnostic. Each SBCE was reviewed using FICE 1. New findings were labeled as either P1 or P2 lesions according to bleeding potential. Patients were followed up to assess the incidence of rebleeding. Results: A total of 42 consecutive patients were included. Sixteen patients (38%) experienced rebleeding after a mean follow-up of 26 months. Review of SBCE images using FICE 1 enabled the identification of previously unrecognized P2 lesions, mainly angioectasias, in nine patients (21%) and P1 lesions, mainly erosions, in 26 patients (62%). Among patients who experienced rebleeding, 13/16 (81%) were diagnosed with P1 lesions with FICE 1 (P=0.043), whereas 3/16 (19%) had confirmed nondiagnostic SBCE and only 1/16 (6%) had newly diagnosed P2 (plus P1) lesions. An alternative source of bleeding outside the small bowel was found in only 3/16 (19%) patients with rebleeding during the follow-up. Conclusion: In a significant proportion of patients with OGIB, FICE 1 may detect potentially bleeding lesions previously missed under conventional white light SBCE. Review of nondiagnostic SBCE with FICE 1 may be a valuable strategy to obviate the need for further investigations in patients with OGIB, particularly for those who experience rebleeding.

PillCam COLON 2© in Crohn's disease: A new concept of pan-enteric mucosal healing assessment

AIM To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease (CD) with a single non-invasive examination, by using PillCam COLON 2 (PCC2). METHODS Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis, patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score (LS). After = 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS < 135. RESULTS Twelve patients were included (7 male; mean age: 32 years), and mean follow-up was 38 mo. The majority of patients (83.3%) received immunosuppressive therapy. Three patients (25%) achieved mucosal healing in both the small bowel and the colon, while disease activity was limited to either the small bowel or the colon in 5 patients (42%). It was possible to observe the entire gastrointestinal tract in 10 of the 12 patients (83%) who underwent PCC2. CONCLUSION Only three patients in sustained corticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.