Chronic renal failure from the English-speaking Caribbean: 2007 data / Fallo renal crónico en el Caribe anglófono: datos del 2007

AIM: Development of the renal registry to include patients at different stages of chronic kidney disease (CKD). BACKGROUND: The 2007 renal registry include cases at different stages of CKD based on the current guidelines according to the National Kidney Foundation (NKF) Kidney Disease Outcome Initiative (K/DOQI) staging. There was an increase in the number of participating countries, with the addition of Antigua and Barbuda, St Lucia and Turks and Caicos. METHODS: Data were collected using a questionnaire form. Data were stored and analysed in Words Excel for Windows or SPSS 12.0. RESULTS: Data were available for Antigua and Barbuda (n = 43), British Virgin Islands (n = 69), Cayman Islands (n = 45), Trinidad and Tobago (n = 564), Jamaica (n = 920), Turks and Caicos (n = 64), St Lucia (n = 51) and Bahamas (n = 121). The registry identified hypertension, diabetes mellitus and Chronic Glomerulonephritis (CGN) as the commonest causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in these countries. The leading cause of death reported was listed as ischaemic heart disease/heart failure, sepsis and cerebrovascular accident. CONCLUSIONS: The majority of patients with CKD and ESRD had hypertension, diabetes mellitus and CGN as the major causes. Collection of data for patients with CKD at different stages was met with some challenges, and resulted in underestimation of the true number of persons with CKD across these Caribbean countries. More emphasis will continue to be placed on improving data collection so the true incidence, prevalence and healthcare burden of CKD is known in the Caribbean. A web based programme is being developed to improve data collection.

OBJETIVO: Desarrollar el registro renal incluyendo pacientes en diferentes etapas de la enfermedad crónica del riñón (ECR). ANTECEDENTES: El registro renal 2007 incluye casos en diferentes etapas de la ECR, sobre la base de los lineamientos actuales de la estadificación según la iniciativa para los resultados de la enfermedad crónica renal (K/DOQI) propuesta por la Fundación Nacional del Riñón (NKF). Hubo un aumento en el número de países participantes, al añadirse Antigua y Barbuda, Santa Lucia e Islas Turcas y Caicos. MÉTODOS: Los datos fueron recogidos utilizando un cuestionario. Luego fueron almacenados y analizados usando Excel para Windows, o mediante SPSS 12.0. RESULTADOS: Hubo a disposición datos para Antigua y Barbuda (n = 43), Islas Vírgenes Británicas (n = 69), Islas Cayman (n = 45), Trinidad y Tobago (n = 564), Jamaica (n = 920), Islas Turcas y Caicos (n = 64), Santa Lucia (n = 51) y Bahamas (n = 121). El registro identificó la hipertensión, la diabetes mellitus y la glomerulonefritis crónica (GNC) como las causas más comunes de la enfermedad crónica del riñón (ECR) y la enfermedad renal terminal (ERT) en estos países. La principal causa de muerte según los reportes, fueron la cardiopatía isquémica/fallo cardíaco, la sepsis y el accidente cardiovascular. CONCLUSIONES: La mayoría de los pacientes con ECR y ERT sufrían de hipertensión, diabetes mellitus y GNC como causas mayores. La recogida de datos para los pacientes con ECR tuvo algunas dificultades, por lo que se subestimó el número real de personas con ECR en todos estos países caribeños. Se seguiría haciendo un mayor énfasis en mejorar la recogida de datos, de modo que la verdadera incidencia, prevalencia y carga de atención a la salud de la ECR sea conocida en el Caribe. Se halla en curso el desarrollo de un programa en la red de Internet, a fin de mejorar la recogida de datos.

Construction and analysis of a metagenomic library from an enhanced biological phosphorus removal biomass.

The enhanced biological phosphorus removal (EBPR) process is regularly used for the treatment of wastewater, but suffers from erratic performance. Successful EBPR relies on the growth of bacteria called polyphosphate-accumulating organisms (PAOs), which store phosphorus intracellularly as polyphosphate, thus removing it from wastewater. Metabolic models have been proposed which describe the measured chemical transformations, however genetic evidence is lacking to confirm these hypotheses. The aim of this research was to generate a metagenomic library from biomass enriched in PAOs as determined by phenotypic data and fluorescence in situ hybridisation (FISH) using probes specific for the only described PAO to date, "Candidatus Accumulibacter phosphatis". DNA extraction methods were optimised and two fosmid libraries were constructed which contained 93 million base pairs of metagenomic data. Initial screening of the library for 16S rRNA genes revealed fosmids originating from a range of nonpure-cultured wastewater bacteria. The metagenomic libraries constructed will provide the ability to link phylogenetic and metabolic data for bacteria involved in nutrient removal from wastewater.

A survey of chronic renal failure in Jamaica.

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conducted at six Jamaican healthcare facilities between July 1998 and December 1999 and included 605 patients with CRF. Men with CRF (57% of patients, mean age of 56.7 years) were significantly older than women (mean age 53.2 years). Hypertension was the most commonly associated medical condition (60.8% of patients) followed by diabetes mellitus (31.4% of patients). The estimated crude point prevalence of CRF in persons 20 years and over at the end of 1999 was 327 per million population. More than one-third of patients with CRF (39%) were receiving renal replacement therapy, the most common modality being haemodialysis, and only 1.8% of patients had received kidney transplantation. The prevalence of chronic renal failure was not increased in areas known to have high soil cadmium levels. Chronic renal failure is a significant public health problem in Jamaica and is placing an increasing financial burden on the healthcare sector.

A survey of chronic renal failure in Jamaica

The prevalence of chronic renal failure (CRF)/end stage renal disease and the accessibility of long term renal replacement therapy in Jamaica were evaluated. The study was conducted at six Jamaican healthcare facilities between July 1998 and December 1999 and included 605 patients with CRF. Men with CRF (57 of patients, mean age of 56.7 years) were significantly older than women (mean age 53.2 years). Hypertension was the most commonly associated medical condition (60.8 of patients) followed by diabetes mellitus (31.4 of patients). The estimated crude point prevalence of CRF in persons 20 years and over at the end of 1999 was 327 per million population. More than one-third of patients with CRF (39) were receiving renal replacement therapy, the most common modality being haemodialysis, and only 1.8 of patients had received kidney transplantation. The prevalence of chronic renal failure was not increased in areas known to have high soil cadmium levels. Chronic renal failure is a significant public health problem in Jamaica and is placing an increasing financial burden on the healthcare sector

Calcium alginate entrapment of the yeast Rhodosporidium toruloides for the kinetic resolution of 1,2-epoxyoctane.

Resting cells of the yeast Rhodosporidium toruloides (UOFS Y-0471) were immobilised in calcium alginate beads for the enantioselective kinetic resolution of racemic-1,2-epoxyoctane. The initial activity exhibited by immobilised cells was almost 50% lower than that of the free counterpart but was extremely stable when compared to the free cells. The concentration of the immobilised biomass had no effect on apparent enzyme activity but did lead to a decrease in single cell activity. An increase in both the alginate and CaCl2 concentrations used for bead preparation led to a decrease in enzyme stability. An increase in the alginate concentration led to an increase in bead diameter. The stoichiometric equation for cross-linking of alginate was only obeyed when CaCl2 concentrations higher than 0.4 M were utilised for bead preparation.

Biocatalysis of nitro substituted styrene oxides by non-conventional yeasts.

Yeast strains (410) from more than 45 different genera were screened for the enantioselective hydrolysis of nitro substituted styrene oxides. These strains included 262 yeasts with known epoxides hydrolase activity for various other epoxides. Epoxide hydrolase activity for p-nitrostyrene oxide (pNSO) (177 strains) and m-nitrostyrene oxide (mNSO) (148 strains) was widespread in the yeasts, while activity for o-nitrostyrene oxide (oNSO) was less ubiquitous (22 strains). The strains that displayed enantioselectivity in the hydrolysis of one or more of the nitro substituted styrene oxides (35 strains) were also screened against styrene oxide (SO). Rhodosporidium toruloides UOFS Y-0471 displayed the highest enantioselectivity for pNSO (ee 55%, yield 35%) while Rhodotorula glutinis UOFS Y-0653 displayed the highest enantioselectivity for mNSO (ee > 98%, yield 29%), oNSO (ee 39%, yield 19%) and SO (ee > 98%, yield 19%). (R)-Styrene oxide was preferentially hydrolysed to the corresponding (R)-diol with retention of configuration at the stereogenic centre. In the case of the nitro substituted styrene oxides the absolute configurations of the remaining epoxides and the formed diols were not established.

Synthesis of N-alkyl substituted indolocarbazoles as potent inhibitors of human cytomegalovirus replication.

The synthesis and antiviral evaluation of unsymmetrical indolocarbazole derivatives of Arcyriaflavin A, substituted with a range of alkyl groups at the indole nitrogen, is described. Structure-activity relationships in this series against human cytomegalovirus (HCMV) replication in cell culture are reported. Compound 4b was identified as potent inhibitor of HCMV (IC(50)=19 nM), which retained activity against a range of HCMV strains including ganciclovir resistant isolates.

Human T-cell lymphotropic virus-1-associated renal disease in Jamaican children.

This report documents the clinicopathological features in two Jamaican children who presented with infective dermatitis, glomerulonephritis, renal failure and human T-cell lymphotropic virus (HTLV-1) seropositivity. Severe hypertension with hypertensive encephalopathy was the most impressive clinical feature. Histological findings from renal biopsy specimens in both cases revealed significant glomerulosclerosis with fibrosis, chronic inflammatory cell infiltrates in the interstitium, and arteriolar hypertensive changes. Membranoproliferative glomerulonephritis (MPGN) was demonstrable in case 1 and marked focal glomerulosclerosis in case 2. Case 1 developed end stage renal failure and died within 3 years of diagnosis. Case 2 remains hypertensive and in chronic renal failure. Although a causal relationship between HTLV-1 infection and renal disease cannot be proven by these two cases, it appears that renal involvement in children with HTLV-1 infection is severe, with the potential for chronic renal failure and malignant hypertension. HTLV-1 nephropathy should be suspected in children with infective dermatitis and renal disease.

Novel forms of ring-hydroxylating dioxygenases are widespread in pristine and contaminated soils.

Ring-hydroxylating dioxygenases (RHDs) are of central importance to bacterial recycling of aromatic hydrocarbons, including anthropogenic pollutants. The database of presently characterized RHDs is biased towards those from organisms readily isolated on anthropogenic substrates. To investigate the extent to which RHDs from extant organisms reflect the natural diversity of these enzymes, we developed a polymerase chain reaction (PCR) method for retrieval of RHD gene fragments from environmental samples. Gene libraries from two contaminated and two pristine soil samples were constructed. None of the inferred peptides from clones examined were identical to previously described RHDs; however, all showed significant sequence homology and contained key catalytic residues. On the basis of sequence identity, the environmental clones clustered into six distinct groups, only one of which included known RHDs. One of the new sequence groupings was particularly widespread, being recovered from all soil samples tested. Comparison of inferred peptide sequences of the environmental clones and known RHDs showed the former to have greater sequence variation at sites thought to influence accessibility of the active site than that seen between currently known RHDs. We conclude that presently characterized RHDs do not adequately represent the diversity of function found in in situ forms.

Characterization of a truncated progesterone receptor protein in breast tumors.

The progesterone receptor (PR) mediates the actions of progesterone in the normal and malignant breast. PR is expressed as two proteins, PR B and PR A, which are expressed in normal progesterone target tissues and in breast cancers. A significant proportion of breast cancers contain, in addition, a smaller PR protein of molecular mass 78 kDa (PR78 kDa). The significance of PR78 kDa expression is unknown, and in particular, there are no data on whether PR78 kDa is able to bind ligand and therefore potentially exhibit transcriptional activity. If this smaller PR species exhibits similar differences in function as have been evidenced in vitro for PR A relative to PR B, it is possible that this PR species may be an important component in determination of progesterone response in breast cancer. The purpose of this study was to determine whether the PR78 kDa protein in breast tumors is able to bind ligand and to determine whether posttranscriptional mechanisms contribute to its formation in breast cancers. There was no evidence that PR78 kDa was derived from proteolytic activity of either PR B or PR A. Similarly, although exon-deleted PR transcripts were detected (which could, if translated, give rise to a PR protein similar in size to PR78 kDa), neither the abundance of such transcripts nor their relationship to levels of expressed PR78 kDa protein supported a role for exon deletion in formation of this truncated PR protein. PR78 kDa was not recognized by an antibody specific for PR B, indicating that, like PR A, it lacks the N-terminal portion of PR. PR78 kDa was able to bind the progestin ligand, indicating that it may have transcriptional activity. In summary, this study has shown that a truncated PR protein, found in breast cancers, is ligand-binding and seems to be derived from PR A, indicating that it may have a role in progesterone signaling, although a deeper understanding of its role, if any, in breast cancer remains to be established.

Methods for microbial DNA extraction from soil for PCR amplification.

Amplification of DNA from soil is often inhibited by co-purified contaminants. A rapid, inexpensive, large-scale DNA extraction method involving minimal purification has been developed that is applicable to various soil types (1). DNA is also suitable for PCR amplification using various DNA targets. DNA was extracted from 100g of soil using direct lysis with glass beads and SDS followed by potassium acetate precipitation, polyethylene glycol precipitation, phenol extraction and isopropanol precipitation. This method was compared to other DNA extraction methods with regard to DNA purity and size.

PCR amplification of crude microbial DNA extracted from soil.

A rapid, inexpensive, large-scale DNA extraction method involving minimal purification has been developed that is applicable to various soil types. DNA was extracted from 100 g of soil using direct lysis with glass beads and sodium dodecyl sulphate (SDS) followed by polyethylene glycol precipitation, potassium acetate precipitation, phenol extraction and isopropanol precipitation. The crude extract could be used in PCR directed at high-copy number (bacterial small subunit rRNA) and single-copy (fungal beta-tubulin) genes.

Progesterone receptor A and B protein expression in human breast cancer.

The human progesterone receptor (PR) is a ligand-activated nuclear transcription factor which mediates progesterone action in target tissues. Two PR proteins, PR A (81-83 kDa) and PR B (116-120 kDa), have been described and different physiological activities ascribed to each on the basis of in vitro studies, suggesting that their ratio of expression may control progesterone responsiveness in target cells. Presence of PR in breast tumors is an important indicator of likely responsiveness to endocrine agents. However, the relative expression of PR A and B in breast cancer has not been described and its clinical significance has not been addressed. We have examined the expression of PR A and B in PR-positive breast tumors and found that while in most tumors PR A and B were expressed in similar amounts there was a broad overall distribution of PR A:B ratio which deviated significantly from a normal log distribution with tumors containing a PR A:B ration greater than 4 being over-represented in the group. Linear regression analysis revealed that high PR A:B ratios, in general, derived from a low concentration of PR B rather than high expression of PR A. PR A:B protein ratios were not correlated with the age of the patient or with total PR concentration. A third PR protein band (PR 78 kDa) was detected which comprised greater than 20% of total PR protein in a quarter of the tumor samples examined. The characteristics of tumors containing PR 78 kDa were not different from the overall group. In summary, in PR-positive breast tumors the ratio of expression of PR A and B proteins is close to unity as is seen in a number of other progestin target tissues. However, a significant proportion of tumors expressed very low levels of PR B and a consequently high PR A:B ration. Although the clinical consequence of this observation is not known, the in vitro findings that PR A may act as a repressor for PR B suggests that tumors containing primarily PR A may identify a subset of patients with low or aberrant response to endocrine agents.

Characterization of progesterone receptor A and B expression in human breast cancer.

The human progesterone receptor (PR) is a ligand-activated nuclear transcription factor that mediates progesterone action in target tissues. Two PR proteins, PR-A (M(r) 81,000-83,000) and PR-B (M(r) 116,000-120,000), have been described and different physiological activities ascribed to each on the basis of in vitro studies, suggesting that their ratio of expression may control progesterone responsiveness in target cells. Presence of PR in breast tumors is an important indicator of likely responsiveness to endocrine agents. However, the relative expression of PR-A and B in breast cancer has not been described, and its clinical significance has not been addressed. Expression of PR-A and B was measured by immunoblot analysis of 202 PR-positive human breast tumor cytosols. The ratio of expression of the two PR proteins (PR-A/B) ranged from 0.04 to 179.3. The median PR-A/B ratio was 1.26, and 61.4% of samples had PR-A/B ratios between 0 and 2. PR-A/B ratios deviated significantly from a normal log distribution; tumors containing a PR-A/B ratio greater than 4 were overrepresented in the group. Linear regression analysis revealed that high PR-A/B ratios, in general, derived from a low concentration of PR-B rather than high expression of PR-A. PR-A/B protein ratios were not correlated with the age of the patient or with total PR concentration. A third PR protein band (PR78kDa) was detected in a number of samples and comprised greater than 20% of total PR protein in 52 (25.7%) of the 202 tumor samples examined. The range or frequency distribution of PR-A/B ratios in samples containing PR78kDa was not different to the overall group. In summary, in PR-positive breast tumors, the ratio of expression of PR-A and B proteins is close to unity, as is seen in a number of other progestin target tissues. However, a significant proportion of tumors expressed very low levels of PR-B and a consequently high PR-A/B ratio. Although the clinical consequence of this observation is not known, the in vitro findings that PR-A may act as a repressor of PR-B suggest that tumors containing primarily PR-A may identify a subset of patients with low or aberrant response to endocrine agents.

Antipneumocystis activity of 17C91, a prodrug of atovaquone.

The prophylactic efficacy of 17C91, a carbamate prodrug of atovaquone (ATQ), was investigated in a severe combined immunodeficient mouse model of Pneumocystis carinii pneumonia (PCP). At an oral dosage equivalent to 100 mg of ATQ per kg of body weight per day, 17C91 protected 9 of 10 mice from PCP and had a prophylactic efficacy comparable to that of co-trimoxazole (at 250 mg of sulfamethoxazole plus 50 mg of trimethoprim per kg per day orally). The intensity of P. carinii infection (infection score) of mice treated with 17C91 correlated with the concentration of ATQ in the plasma, with clearance of the infection associated with plasma ATQ levels of >35 micrograms/ml. 17C91 given orally provided enhanced levels of ATQ in the plasma compared with the conventional ATQ formulation. Additional studies reported in this paper demonstrate that the prophylactic activity of 17C91 against PCP in severe combined immunodeficient mice is comparable to that of a new oral microparticulate formulation of ATQ.

The galileo venus encounter.

The Galileo spacecraft passed Venus on its way to Jupiter on 10 February 1990, less than 4 months after launch from Earth aboard the shuttle Atlantis. Because Galileo's instruments were selected for broad-based planetary exploration, the spacecraft was able to obtain a wide range of measurements during the Venus encounter. Together with ground-based observations conducted during the encounter, these observations have yielded more accurate information about the planet's plasma environment, cloud patterns, and the possible existence of lightning.

Plasma observations near jupiter: initial results from voyager 1.

Extensive measurements of low-energy positive ions and electrons were made throughout the Jupiter encounter of Voyager 1. The bow shock and magneto-pause were crossed several times at distances consistent with variations in the upstream solar wind pressure measured on Voyager 2. During the inbound pass, the number density increased by six orders of magnitude between the innermost magnetopause crossing at approximately 47 Jupiter radii and near closest approach at approximately 5 Jupiter radii; the plasma flow during this period was predominately in the direction of corotation. Marked increases in number density were observed twice per planetary rotation, near the magnetic equator. Jupiterward of the Io plasma torus, a cold, corotating plasma was observed and the energylcharge spectra show well-resolved, heavy-ion peaks at mass-to-charge ratios A/Z* = 8, 16, 32, and 64.

Observations at mercury encounter by the plasma science experiment on mariner 10.

A fully developed bow shock and magnetosheath were observed near Mercury, providing unambiguous evidence for a strong interaction between Mercury and the solar wind. Inside the sheath there is a distinct region analogous to the magnetosphere or magnetotail of Earth, populated by electrons with lower density and higher temperature than the electrons observed in the solar wind or magnetosheath. At the time of encounter, conditions were such that a perpendicular shock was observed on the inbound leg and a parallel shock was observed on the outbound leg of the trajectory, and energetic plasma electron events were detected upstream from the outbound shock crossing. The interaction is most likely not atmospheric, but the data clearly indicate that the obstacle to solar wind flow is magnetic, either intrinsic or induced. The particle fluxes and energy spectra showed large variations while the spacecraft was inside the magnetosphere, and these variations could be either spatial or temporal.