A 'Full House' Glomerulopathy in a Patient with Multiple Lentigines Syndrome: A Case Report / Glomerulopatía 'full house' en un paciente con síndrome de lentigos múltiples: un reporte de caso

ABSTRACT Multiple lentigines syndrome (MLS) is an autosomal dominant disease which is usually diagnosed clinically by the presence of characteristic features. The molecular genetic testing is an adjuvant diagnostic tool to identify the mutation of particular genes such as PTPN11 genes, RAF1, BRAF or MAP2K1 genes. This syndrome was formerly known as LEOPARD syndrome or Noonan syndrome with multiple lentigines. 'LEOPARD syndrome ' is an acronym of characteristic features (Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of the genitalia, Retardation of growth, and Deafness). There was no previous case report about any glomerulonephropathy in association with MLS. We present a case of a patient with MLS with recurrent nephrotic syndrome who was found to have histologic evidence of 'full house ' glomerulopathy.

RESUMEN El síndrome de lentigos múltiples (SLM) es una enfermedad autosómica dominante que de modo general se diagnostica clínicamente por la presencia de rasgos característicos. La prueba genética molecular es una herramienta de diagnóstico auxiliar utilizada para identificar la mutación de genes específicos tales como los genes PTPN11, RAF1, BRAF, o los genes MAP2K1. Este síndrome se conocía anteriormente como síndrome del leopardo o síndrome de Noonan con múltiples lentigos. El síndrome toma su nombre del acrónimo en inglés LEOPARD, que describe sus rasgos característicos (L lentigos; E conducción electrocardiográfica de las anormalidades; O hipertelorismo ocular; P estenosis pulmonar; A anormalidades de los genitales; R retardo del crecimiento; y D deafness, 'sordera ' en inglés), y que fuera introducido por Gorlin et al en 1969. No existía ningún reporte de caso anterior sobre glomerulonefropatía asociada con SLM. Presentamos el caso de un paciente con SLM con síndrome nefrótico recurrente en el que se halló evidencia histológica de glomerulopatía 'full house'.

A surge of light at the birth of a supernova.

It is difficult to establish the properties of massive stars that explode as supernovae. The electromagnetic emission during the first minutes to hours after the emergence of the shock from the stellar surface conveys important information about the final evolution and structure of the exploding star. However, the unpredictable nature of supernova events hinders the detection of this brief initial phase. Here we report the serendipitous discovery of a newly born, normal type IIb supernova (SN 2016gkg), which reveals a rapid brightening at optical wavelengths of about 40 magnitudes per day. The very frequent sampling of the observations allowed us to study in detail the outermost structure of the progenitor of the supernova and the physics of the emergence of the shock. We develop hydrodynamical models of the explosion that naturally account for the complete evolution of the supernova over distinct phases regulated by different physical processes. This result suggests that it is appropriate to decouple the treatment of the shock propagation from the unknown mechanism that triggers the explosion.

Level of asthma control and healthcare utilization in Latin America.

The purpose of this study was to investigate whether uncontrolled asthma was associated with healthcare outcomes among Latin American patients with asthma. We used data from 2168 patients with asthma who participated in the 2011 Latin America Asthma Insights and Management (AIM) survey. Using Global Initiative for Asthma (GINA) guidelines, patients were categorized as having asthma that was well-controlled, partly controlled, or uncontrolled. Overall, 7% of the patients surveyed had asthma that was classified as well-controlled. Patients whose asthma was not well-controlled were significantly more likely to report use of asthma medications (ORs ranging from 1.6-41) and to have had emergency healthcare visits or hospitalizations for their asthma in the previous year (ORs ranging from 2.1 to 5.9). They also reported decreases in their productivity compared to patients with well-controlled asthma. These associations suggest that emphasis on improving asthma control could have substantial effects on patient productivity and utilization of healthcare resources.

Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis.

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004

Fibrous dysplasia of the jaw bone: a review of 15 new cases and two cases of recurrence in Jamaica together with a case report

The authors reviewed 15 new cases of fibrous dysplasia of the jaw bone and two cases of recurrence seen in Jamaica between 1980 and 1995. Only cases which had a histological confirmation of fibrous dysplasia were included. The clinical behaviour and radiological findings of these cases were studied from the case files, either at the Cornwall Regional Hospital or the Kingston Public Hospital in Jamaica (AU)

Fibrous dysplasia of the jaw bone: a review of 15 new cases and two cases of recurrence in Jamaica together with a case report.

The authors reviewed 15 new cases of fibrous dysplasia of the jaw bone and two cases of recurrence seen in Jamaica between 1980 and 1995. Only cases which had a histological confirmation of fibrous dysplasia were included. The clinical behaviour and radiological findings of these cases were studied from the case files, either at the Cornwall Regional Hospital or the Kingston Public Hospital in Jamaica.

Fibrous dysplasia of the jaw bone in Jamaica: a review of 15 new cases and 2 cases of recurrence together with a case report - abstract

The authors review 15 new cases of fibrous dysplasia of the jaw bone and two cases of recurrence seen in Jamaica between 1980 and 1995, a period of 15 years. Only cases which had histological confirmation to be fibrous dysplasia were included. The clinical behaviour and radiological findings of these cases were studied from the case files, either at the Cornwall Regional Hospital or the Kingston Public Hospital in Jamaica. The present series of 15 new cases of fibrous dysplasia and 2 cases of recurrent fibrous dysplasia of the jaw bone are the first to be documented in Jamaica, accounting for 5.2 percent and 0.68 percent, respectively, of jaw bone tumours in Jamaica. Fibrous dysplasia (excluding recurrent fibrous dysplasia) accounted for 47 percent of all cases of fibro-osseus lesions (WHO classification) seen in Jamaica and recurrent fibrous dysplasia accounted for 6.2 percent of all cases of fibro-osseous lesions seen in Jamaica during this period. One case of fibrous dysplasia presented atypically and is reported in this paper. For the new cases of monostotic fibrous dysplasia, the patients were between the ages of 10 and 47 years, two cases were patients aged 47 years at the time of presentation; this is atypical of what has been previously documented to be the average age at presentation. For these reasons there is need for further study of more new cases in Jamaica. (AU)

Epidemiology of human immunodeficiency virus infection in Central Americans treated in Harris County, Texas Hospital District facilities.

The prevalence of human immunodeficiency virus (HIV) infection among Central Americans is increasing. The purpose of this study was to describe the epidemiology of HIV infection among local Central American immigrants in the United States. Medical records of HIV-infected Central Americans treated at Harris County Hospital District (HCHD) facilities, the major source of indigent care in Houston, Texas, were retrospectively reviewed. Between January 1, 1990 and February 28, 1995, 18,156 Central Americans were seen at HCHD facilities, of whom 56 (13 females and 43 males) were identified as HIV-infected (0.3% versus 1.3% of all locally treated patients; P < 0.001, by test of binomial proportions). Most were from Honduras (n = 25) or El Salvador (n = 23). The mean age was 28.7 years, the mean CD4+ lymphocyte count at presentation was 173 cells/mm3, and 36 (64%) had acquired immunodeficiency syndrome (AIDS) at presentation. The 13 women (23% versus 22% for all locally treated HIV patients) were disproportionately Honduran (10 of 25 Hondurans versus 3 of 31 other Central Americans; P = 0.011). The HIV risk factors included heterosexuality in 46%, homosexuality in 29%. and a history of injection drug use in 7% (versus 10%, 57%, and 34%, respectively, for all locally treated HIV patients). The 76 diagnosed opportunistic infections (OIs) included a disproportionately greater number of patients with tuberculosis (n = 14, 33% versus 6% of all locally treated AIDS patients), toxoplasmosis (n = 10, 24% versus 7%), and cryptococcal meningitis (n = 9, 21% versus 7%), and a lower number of patients with pneumocystosis (n = 12, 29% versus 43%) and candida esophagitis (n = 2, 5% versus 16%). Central American immigrants infected with HIV present with relatively advanced disease, and the most frequent OIs are diseases for which effective prophylaxis exists. Targeted HIV screening and early intervention in this group are warranted.

Radiology of ameloblastoma in Jamaica

AIMS: The radiographic characteristics of ameloblastoma are presented for 47 primary and 12 recurrent lesions found in Jamaica. While ameloblastoma is well-documented elsewhere in the world, this is not the case for Jamaica. MATERIAL AND METHODS: All cases of histologically confirmed ameloblastoma seen in Jamaica between 1980 and 1995 were reviewed with special attention being paid to the radiologic appearance. RESULTS: Twenty-seven (57 percent) of the primary cases were multilocular radiolucencies while 43 percent were unilocular and radiologically well defined. Root resorption was found in most instances irrespective of the presence of internal septae. Forty-four cases (94 percent) involved the mandible, with one presenting bilaterally and almost symmetrically in the posterior mandible. Three cases involved the maxilla of which one also involved the mandible on the same side, a case of unilateral involvement of both mandible and maxilla in the same patient. Recurrent ameloblastoma presented as cystic unilocular or multilocular radiolucencies of the mandible in the are mesial or distal to the operation site, and extension within the bone graft was also found. CONCLUSIONS: The appearance of ameloblastoma in Jamaica, with few exceptions, is similar to that described elsewhere.(AU)

A 15-year study of jaw bone tumours in Jamaica (1980-1995) with specific emphasis on radiology

Jaw-bone tumours were studied retrospectively from data obtained from the Department of Oral and Maxillofacial Surgery at both the Kingston Public Hospital and the Cornwall Regional Hospital in Jamaica . In this study special emphasis was placed on the radiological aspect of jaw-bone tumours. As far as we are aware, no such study has been previously carried out in the English speaking Caribbean. This study is of great interest because it utilizes previously unreported clinical materials to document aspects of jaw-bone tumours in Jamaica which will allow for a comparison with what has previously been documented by other authors throughout the world. A computer programme called "Tumour Power House" was developed to be used on an IBM or Macintosh computer, for use on a continuous basis for tumour registering. A total of 293 jaw-bone tumours has currently been analysed with special emphasis on radiology. Jaw-bone tumours of odontogenic origin accounted for 42 percent of all jaw-bone tumours in Jamaica. Of these, 70 (57 percent) were odontogenic tumours and 42 (34 percent) were odontogenic cysts. The 32 cases of fibro-osseous lesions during this period represents approximately 11 percent of the total number of jaw-bone tumours in Jamaica. Of the 32 cases of fibro-osseous lesions 15 (47 percent), were fibrous dysplasia and surprisingly, three cases (9.4 percent) were gigantiform cementoma, thus adding to the few numbers in the literature. No case of cementifying fibroma was recorded (AU)

The first report of familial adult T-cell leukaemia lymphoma in the United Kingdom.

We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older sibling had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents the development of ATLL in second-generation Caribbean immigrants.

Nippostrongylus brasiliensis: ability of plasma to prime free radical generation by leukocytes in response to adult worms not due to gamma-interferon or tumour necrosis factor.

Plasma-borne factors prime leukocytes from both infected and uninfected rats for radical generation in response to N. brasiliensis. The concentration of these factors is increased following infection and reaches maximal levels on day 8 post-infection (p.i.) as demonstrated by the striking ability of plasma from infected rats to prime leukocytes from uninfected rats to produce free radicals in response to adult worms. The cytokines, gamma-interferon and tumour necrosis factor (TNF) can be detected in plasma during infection with a variety of organisms and several lines of immunological and pathophysiological evidence, including radical generation, weight loss, anaemia and diarrhoea, implicate generation of these proteins in response to infection with N. brasiliensis. We therefore investigated whether gamma-interferon and TNF were detectable in the plasma of rats infected with N. brasiliensis and whether the presence of these cytokines correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis. However, gamma-interferon was not detected in the plasma of rats at any time after infection with N. brasiliensis and neutralizing monoclonal antibody to rat gamma-interferon had no effect on the ability of plasma to prime free radical generation. TNF was detected in the plasma of heavily-infected rats but only at very low levels (< 1 ng/ml), though copius in vivo synthesis of TNF could be induced by treatment of the infected rats with lipopolysaccharide (LPS). However, neither parasite-induced nor parasite plus LPS-induced plasma TNF correlated with the ability of plasma to enhance radical generation in response to N. brasiliensis.(ABSTRACT TRUNCATED AT 250 WORDS)

Free radical generation and the course of primary infection with Nippostrongylus brasiliensis in congenitally athymic (nude) rats.

The course of primary infections with Nippostrongylus brasiliensis was followed in nude (CBH/R nu/nu) and heterozygote (CBH/R nu/+) rats. In both nude and heterozygote rats peak egg production by N. brasiliensis occurred on days 7 and 8 post-infection. However, whereas in heterozygote rats egg production declined rapidly thereafter and ceased completely by day 14 post-infection, in nude rats high numbers of N. brasiliensis eggs were still seen on day 27 post-infection, when the experiment was terminated. In comparison with the nude rats, heterozygote rats had a 5-fold greater loss of weight by day 9 post-infection and a 4-fold higher incidence of diarrhoea. Furthermore, infected heterozygote rats became anaemic whereas uninfected rats and infected nude rats showed no evidence of anaemia. Free radical generation was measured in infected (9 days) and uninfected rats. Leucocytes from infected heterozygote rats were able to generate copious quantities of free radicals in response to N. brasiliensis whereas leucocytes from infected nude rats produced only slightly more free radicals than uninfected rats. Thus, worm rejection, weight loss, diarrhoea, anaemia and free radical generation in response to N. brasiliensis infection are all T-cell dependent events.

A role for protein kinase C in the production of free oxygen radicals in response to Nippostrongylus brasiliensis.

The involvement of protein kinase C in the initiation of free oxygen radical generation by rat leukocytes in response to the nematode Nippostrongylus brasiliensis was investigated. Inhibitors of protein kinase C, trifluoperazine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), inhibited free radical generation in response to N. brasiliensis in vitro. Neither inhibitor affected free radical generation by the cell-free xanthine/xanthine oxidase system, indicating that the agents did not scavenge free radicals; they also failed to affect leukocyte viability. Furthermore, activators of protein kinase C, the calcium ionophore A23187 and the diacylglycerol 1-oleoyl-2-acetyl-rac-glycerol (OAG), enhanced free radical generation by leukocytes in response to N. brasiliensis in vitro. Thus, protein kinase C apparently plays an important role in the initiation of free radical generation in response to N. brasiliensis; since free radicals may play a critical role in worm expulsion, this implies that protein kinase C may also be important in the rejection of N. brasiliensis from the small intestine of the rat.

Identification of multiple associative and dissociative proliferative and uveitogenic T-cell sites in human interstitial retinoid-binding protein.

Human interstitial retinoid-binding protein (HIRBP) is a 136 kDa retinal protein capable of inducing experimental autoimmune uveoretinitis (EAU) and experimental autoimmune pinealitis (EAP) in Lewis (LEW) rats. In order to identify the T-cell recognition sites of HIRBP responsible for uveitogenic and proliferative responses, 125 overlapping peptides corresponding to its entire 1262 amino acid sequence were synthesized. Individual peptides were tested for their ability to induce EAU in LEW rats and to stimulate lymphocyte proliferation in rats immunized with the native molecule. Our previous results showed the presence of nine uveitogenic peptides in HIRBP with a minimum requirement of eight amino acids needed to induce EAU in LEW rats. Our present studies show nine proliferative peptides, four of which are also responsible for uveitogenicity. Another four peptides known to actively induce EAU were unable to elicit proliferative responses. However, these peptides overlapped or were adjacent to peptides that elicited good proliferative responses. A single, highly proliferative peptide was located on the amino terminus of HIRBP. In addition, EAU was adoptively transferred with lymph node cells (LNC) of LEW rats previously immunized with two synthetic peptides known to be uveitogenic. Our study indicates that human IRBP is a complex molecule containing multiple and spatially distinct T-cell epitopes responsible for its uveitogenicity, adoptive transfer of EAU and proliferative responses.

Free radical generation during primary infections with Nippostrongylus brasiliensis.

The production of free radicals during infection of the rat with Nippostrongylus brasiliensis was investigated. Lipid peroxidation, which is the best documented effect of free radicals, was monitored in the small intestines of infected rats by measurement of malonyldialdehyde and was found to be increased at the time of worm rejection. The capacity of peritoneal leucocytes to produce free radicals, as measured by chemiluminescence, was monitored in rats infected with different doses of N. brasiliensis. Rejection of N. brasiliensis from rats infected with 6000 third-stage larvae (L3) began 2 days earlier than in rats infected with only 600 L3. Maximal free radical generation also occurred 2 days earlier and was quantitatively greater in rats infected with 6000 L3. Free radical generation by leucocytes in response to live adult N. brasiliensis was enhanced by plasma from infected rats indicating the existence of a plasma-borne factor responsible for the initiation of free radical generation in response to N. brasiliensis.

The effect of antioxidants on the rejection of Nippostrongylus brasiliensis.

The effect of the antioxidants, butylated hydroxy anisole (BHA) and vitamin E, on the rejection of Nippostrongylus brasiliensis from the small intestine of the rat was investigated. Worm expulsion was inhibited by BHA. Malonyldialdehyde production in the small intestines and free radical generation by peritoneal leucocytes from infected rats were also inhibited by BHA. Vitamin E, although inhibiting malonyldialdehyde production, did not prevent worm expulsion. Significantly, vitamin E was much less effective than BHA at reducing free radical generation by rat leucocytes in response to N. brasiliensis.

The role of free oxygen radicals in the expulsion of primary infections of Nippostrongylus brasiliensis.

The many and varied pathological, immunological and physiological manifestations of infection with Nippostrongylus brasiliensis may be unified by considering the role of leukocyte-generated free oxygen radicals in worm expulsion. Aside from directly damaging the adult stage of N.brasiliensis and possibly leading to its elimination from the small intestine, free radicals may also damage intestinal cells, thereby contributing to the gut pathology characteristic of infection. gamma-Interferon (and possibly tumour necrosis factor) may be involved in the initiation of free radical generation in response to N. brasiliensis and may also contribute to various side effects of infection such as hypertriglyceridaemia and cachexia. gamma-Interferon may initiate free radical generation via the agency of protein kinase C, an enzyme that can induce various additional responses including lysosomal enzyme and amine secretion and arachidonic acid metabolism. The possible interactions between these mediators and free radicals are subtle and diverse and may profoundly affect the course of infection.