Odonto-ungueal dysplasia: an apparently new autosomal dominant ectodermal dysplasia

We describe 27 subjects (11 women) from five generations of a family with an apparently hitherto undescribed ectodermal dysplasia. All of them presented dental and/or nail alterations only. A genetic analysis of the family suggests an autosomal dominant gene. Differential diagnosis considered eight conditions belonging to the same odonto-onychic (2-3) subgroup, as well as Fried's tooth and nail syndrome and hypodontia and nail dysgenesis (both in 1-2-3 subgroup).

Renal and extrarenal manifestations of autosomal dominant polycystic kidney disease

The objective of the present study was to determine the frequency of the most common clinical features in patients with autosomal dominant polycystic kidney disease in a sample of the Brazilian population. The medical records of 92 patients with autosomal dominant polycystic kidney disease attended during the period from 1985 to 2003 were reviewed. The following data were recorded: age at diagnosis, gender, associated clinical manifestations, occurrence of stroke, age at loss of renal function (beginning of dialysis), and presence of a family history. The involvement of abdominal viscera was investigated by ultrasonography. Intracranial alterations were prospectively investigated by magnetic resonance angiography in 42 asymptomatic patients, and complemented with digital subtraction arteriography when indicated. Mean age at diagnosis was 35.1 ± 14.9 years, and mean serum creatinine at referral was 2.4 ± 2.8 mg/dL. The most frequent clinical manifestations during the disease were arterial hypertension (63.3%), lumbar pain (55.4%), an abdominal mass (47.8%), and urinary infection (35.8%). Loss of renal function occurred in 27 patients (mean age: 45.4 ± 9.5 years). The liver was the second organ most frequently affected (39.1%). Stroke occurred in 7.6% of the patients. Asymptomatic intracranial aneurysm was detected in 3 patients and arachnoid cysts in 3 other patients. In conclusion, the most common clinical features were lumbar pain, arterial hypertension, abdominal mass, and urinary infection, and the most serious complications were chronic renal failure and stroke. Both intracranial aneurysms and arachnoid cysts occurred in asymptomatic patients at a frequency of 7.14%.

Interaction between growth differentiation factor 9, insulin-like growth factor I and growth hormone on the in vitro development and survival of goat preantral follicles

The objective of this study was to determine the effects of GDF-9, IGF-I, and GH alone or combined on preantral follicle survival, activation and development after 1 and 7 days of in vitro culture. Either fresh (non-cultured) or cultured ovarian tissue was processed for histological and fluorescence analysis. For all media tested, the percent of normal follicles was greater when compared to minimum essential medium supplemented (MEM+) alone, except when ovarian tissue was cultured with GDF-9/IGF-I or GDF-9/GH (P < 0.05). Fluorescence analysis showed that the percent of viable follicles after 7 days of culture was similar for non-cultured tissue and for all treatments tested. The percent of primordial follicles was reduced (P < 0.05) and there was a significant and concomitant increase in the percent of intermediate and primary follicles in all treatments tested after 7 days of culture when compared to non-cultured tissue. After 7 days of culture, the highest percent of intermediate follicles was observed with IGF-I/GH (61.3%), and the highest percent of primary follicles was achieved with IGF-I (57.7%). After 7 days of culture in MEM+ containing GDF-9, IGF-I and GH alone or in all associations, a significant increase in follicular diameter was observed when compared to MEM+ alone and non-cultured tissue. In conclusion, GDF-9, IGF-I and GH alone or in combination maintain preantral follicle survival and promote primordial follicle activation. Nevertheless, the data showed that IGF-I/GH and IGF-I alone are efficient in promoting the transition from primordial to intermediate follicles and from intermediate to primary follicles, respectively.

Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC2 is a non-selective cation channel permeable to Ca2+, while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca2+ signaling. The intracellular Ca2+ homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin (mTOR) and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.

Caffeine intake by patients with autosomal dominant polycystic kidney disease

Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD), we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years) and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years). The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day), and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day), the renal volume was not directly associated with caffeine intake.

Phytohemagglutinin improves the development and ultrastructure of in vitro-cultured goat (Capra hircus) preantral follicles

The objective this study was to determine the effect of phytohemagglutinin (PHA) on survival, growth and gene expression in caprine secondary follicles culturedin vitro. Secondary follicles (∼0.2 mm) were isolated from the cortex of caprine ovaries and cultured individually for 6 days in α-MEM+ supplemented with PHA (0, 1, 10, 50, 100, or 200 µg/mL). After 6 days of culture, follicle diameter and survival, antrum formation, ultrastructure and expression of mRNA for FSH receptors (FSH-R), proliferating cell nuclear antigen (PCNA), and neuronal nitric oxide synthase were determined. All treatments maintained follicular survival [α-MEM+ (94.59%); 1 µg/mL PHA (96.43%); 10 µg/mL PHA (84.85%); 50 µg/mL PHA (85.29%); 100 µg/mL PHA (88.57%), and 200 µg/mL PHA (87.50)], but the presence of 10 µg/mL PHA in the culture medium increased the antrum formation rate (21.21%) when compared with control (5.41%, P < 0.05) and ensured the maintenance of oocyte and granulosa cell ultrastructures after 6 days of culture. The expression of mRNA for FSH-R (2.7 ± 0.1) and PCNA (4.4 ± 0.2) was also significantly increased in follicles cultured with 10 µg/mL PHA in relation to those cultured in α-MEM+ (1.0 ± 0.1). In conclusion, supplementation of culture medium with 10 µg/mL PHA maintains the follicular viability and ultrastructure, and promotes the formation of antral cavity after 6 days of culture in vitro.

Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.

Pain determinants of pain in autosomal dominant polycystic kidney disease

Pain is the most common symptom reported by ADPKD patients, afflicting approximately 60% of cases and may result from renal hemorrhage, calculi, urinary tract infections, cyst rupture, or due to stretching of the capsule or traction of the renal pedicle. We have recently investigated pain patterns in AD-PKD patients using a translated version of a pain questionnaire specific for AD-PKD population. The questionnaire revealed that 67% patients with ADPKD exhibited some type of pain. The findings of that study emphasized that pain appeared early in the course of ADPKD, when patients still exhibited preserved renal function. In the present study, a multivariate logistic regression analysis disclosed that renal volume (9-fold increased risk) and nephrolithiasis (4-fold increased risk) were the most important determinant factors for pain in ADPKD patients with preserved renal function, after adjustments for the presence of hypertension and duration of the disease.

Knowledge cities: a taxonomy for analyzing software and information service clusters

Software and information services (SIS) have become a field of increasing opportunities for international trade due to the worldwide diffusion of a combination of technological and organizational innovations. In several regions, the software industry is organized in clusters, usually referred to as "knowledge cities" because of the growing importance of knowledge-intensive services in their economy. This paper has two primary objectives. First, it raises three major questions related to the attractiveness of different cities in Argentina and Brazil for hosting software companies and to their impact on local development. Second, a new taxonomy is proposed for grouping clusters according to their dominant business segment, ownership pattern and scope of operations. The purpose of this taxonomy is to encourage further studies and provide an exploratory analytical tool for analyzing software clusters.

Studies on mosquitoes (Diptera: Culicidae) and anthropic environment: 1- Parity of blood seeking Anopheles (Kerteszia) in South-Eastern Brazil

Populations of Anopheles (Kerteszia) were sampled fortnightly over a one-year period (August 1991 to July 1992) at Ribeira Valley, S. Paulo State, Brazil. Indoor and outdoor collections were made on human bait at evening crepuscular period. The Polovodova technique for age grading was applied to 3,501 females of Anopheles cruzii and to 416 females of An. bellator. That sample represented 34.4% of the total number of mosquitoes collected. The most abundant species found was An. cruzii. However, An. bellator showed an endophagy that was almost three times greater than that of An. cruzii. The overall parous rate was 25.4% and uniparity was practically dominant one. A proportion of 26.9% of An. cruzii and 12.0% of An. bellator were found to be uniparous. Only three outdoor females of the former species (0.1%) showed biparity. Parity of An. cruzii was higher in females caught outdoors than in those caught indoors. Nevertheless, 497 nulliparous females examined (417 cruzii and 80 bellator) had ovaries that had advanced to Christophers and Mer stages III to V. These results imply that these females had already practised hematophagy. Relating these results to those from the parous females, a high statistical significance was found, leading to the conclusion that gonothophic discordance is a common pattern among these anophelines. Further, these results obtained with human bait catches strongly suggest that nearly 38.0% of these host-seeking females had already taken at least one previous blood-meal. So it is possible that enough time could thus be available for the plasmodian development in the vectors.

Economic analysis of surgical treatment of hip fracture in older adults

OBJECTIVE To analyze the incremental cost-utility ratio for the surgical treatment of hip fracture in older patients.METHODS This was a retrospective cohort study of a systematic sample of patients who underwent surgery for hip fracture at a central hospital of a macro-region in the state of Minas Gerais, Southeastern Brazil between January 1, 2009 and December 31, 2011. A decision tree creation was analyzed considering the direct medical costs. The study followed the healthcare provider’s perspective and had a one-year time horizon. Effectiveness was measured by the time elapsed between trauma and surgery after dividing the patients into early and late surgery groups. The utility was obtained in a cross-sectional and indirect manner using the EuroQOL 5 Dimensions generic questionnaire transformed into cardinal numbers using the national regulations established by the Center for the Development and Regional Planning of the State of Minas Gerais. The sample included 110 patients, 27 of whom were allocated in the early surgery group and 83 in the late surgery group. The groups were stratified by age, gender, type of fracture, type of surgery, and anesthetic risk.RESULTS The direct medical cost presented a statistically significant increase among patients in the late surgery group (p < 0.005), mainly because of ward costs (p < 0.001). In-hospital mortality was higher in the late surgery group (7.4% versus 16.9%). The decision tree demonstrated the dominance of the early surgery strategy over the late surgery strategy: R$9,854.34 (USD4,387.17) versus R$26,754.56 (USD11,911.03) per quality-adjusted life year. The sensitivity test with extreme values proved the robustness of the results.CONCLUSIONS After controlling for confounding variables, the strategy of early surgery for hip fracture in the older adults was proven to be dominant, because it presented a lower cost and better results than late surgery.

Advances and challenges in oral health after a decade of the “Smiling Brazil” Program

ABSTRACT OBJECTIVE To analyze oral health work changes in primary health care after Brazil’s National Oral Health Policy Guidelines were released. METHODS A literature review was conducted on Medline, LILACS, Embase, SciELO, Biblioteca Virtual em Saúde, and The Cochrane Library databases, from 2000 to 2013, on elements to analyze work changes. The descriptors used included: primary health care, family health care, work, health care policy, oral health care services, dentistry, oral health, and Brazil. Thirty-two studies were selected and analyzed, with a predominance of qualitative studies from the Northeast region with workers, especially dentists, focusing on completeness and quality of care. RESULTS Observed advances focused on educational and permanent education actions; on welcoming, bonding, and accountability. The main challenges were related to completeness; extension and improvement of care; integrated teamwork; working conditions; planning, monitoring, and evaluation of actions; stimulating people’s participation and social control; and intersectorial actions. CONCLUSIONS Despite the new regulatory environment, there are very few changes in oral health work. Professionals tend to reproduce the dominant biomedical model. Continuing efforts will be required in work management, training, and permanent education fields. Among the possibilities are the increased engagement of managers and professionals in a process to understand work dynamics and training in the perspective of building significant changes for local realities.

Histopathology and immunocytochemical study of type 3 and type 4 complement receptors in the liver and spleen of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi

The objective of this study was to compare the histopathological changes and expression of CR3 and CR4 in the liver and spleen of dogs naturally and experimentally infected with L. chagasi. The basic histopathological lesions observed mainly in naturally infected dogs were: epithelioid hepatic granulomas, hyperplasia and hypertrophy of Kupffer cells, Malpigui follicles and mononucleated cells of the red pulp of the spleen. Sections from the liver and spleen by immunocytochemistry technique showed the presence of CD11b,c\CD 18 antigens in the control and infected animals and no qualitative or quantitative differences in the liver. Nevertheless, CD18 was always increased in the spleen of naturally and experimentally infected dogs. These results indicate that there is a difference in the activaton of CD 18 in both experimental and natural cases of canine visceral leishmaniasis that should play an important role in the immunological response to Leishmania chagasi infection.

Paracoccidioides cerebriformis Moore, 1935. MYCOLOGIC AND IMMUNOCHEMICAL STUDY

The present study concern on mycologic and immunochemical data obtained from two samples of a fungus considered as belonging to the species Paracoccidioides cerebriformis described by Moore in 1935, and maintained since then on Sabouraud’s agar in the mycology collection of the Instituto de Medicina Tropical de São Paulo. After 60 years, the samples exhibited the same characteristics described by Moore (1935). However, experimental lesions did not resulted in guinea-pigs inoculated intratesticularly. The dominant antigen in Paracoccidioides brasiliensis, 43 kDa glicoprotein (gp43), could not be demonstrated by SDS PAGE and Western blotting. Immunoelectrophoresis did not demonstrated the E arch of cathodic migration using a policlonal anti gp43 serum. According to these findings, it is concluded that the fungus described by Moore (1935) as P. cerebriformis does not belong to the genus Paracoccidioides. Paracoccidioidomycosis should therefore be considered as resulting from infection by a single species, Paracoccidioides brasiliensis (Splendore, 1912) as asserted by Almeida (1930). Further studies, through molecular biology methods, could identify the mentioned fungus

Antemortem diagnosis of human rabies in a veterinarian infected when handling a herbivore in Minas Gerais, Brazil

The Ministry of Health's National Human Rabies Control Program advocates pre-exposure prophylaxis (PEP) for professionals involved with animals that are at risk of contracting rabies. We report an antemortem and postmortem diagnosis of rabies in a veterinarian who became infected when handling herbivores with rabies. The antemortem diagnosis was carried out with a saliva sample and a biopsy of hair follicles using molecular biology techniques, while the postmortem diagnosis used a brain sample and conventional techniques. The veterinarian had collected samples to diagnose rabies in suspect herbivores (bovines and caprines) that were subsequently confirmed to be positive in laboratory tests. After onset of classic rabies symptoms, saliva and hair follicles were collected and used for antemortem diagnostic tests and found to be positive by RT-PCR. Genetic sequencing showed that the infection was caused by variant 3 (Desmodus rotundus), a finding confirmed by tests on the brain sample. It is essential that professionals who are at risk of infection by the rabies virus undergo pre-exposure prophylaxis. This study also confirms that molecular biology techniques were used successfully for antemortem diagnosis and therefore not only allow therapeutic methods to be developed, but also enable the source of infection in human rabies cases to be identified accurately and quickly.