Summary The role of two common polymorphisms of enzymes involved in the metabolism of drugs and carcinogens was studied in relation to prostate cancer. The gene encoding one of these enzymes (NAT2) is located in an area where frequent allelic loss occurs in prostate cancer. Mutations at the genes CYP2D6 and NAT2 were analysed by allele-specific polymerase chain reaction and restriction mapping in DNA from 94 subjects with prostate cancer and 160 male healthy control subjects. Eleven prostate specimens were analysed for genotype and enzymatic activities NAT2, CYP2D6 and CYP3A by using the enzyme-specific substrates sulphamethazine and dextromethorphan. Enzyme activities with substrate specificities corresponding to NAT2, CYP2D6 and CYP3A are present in human prostate tissue, with mean ± s.d. activities of 4.8 ± 4.4 pmol min-' mg-' protein, 156 ± 91 and 112 ± 72 nmol min-' mg-' protein respectively. The Km, values for the prostate CYP2D6 and CYP3A enzyme activities corresponded to that of liver CYP2D6 and CYP3A activities, and the CYP2D6 enzyme activity is related to the CYP2D6 genotype. The N-acetyftransferase, in contrast, had a higher Km than NAT2 and was independent of the NAT2 genotype. The CYP2D6 and CYP3A enzymes, and an N-acetyttransferase activity that is independent of the regulation of the NAT2 gene. are expressed in human prostate tissue. The presence of carcinogen-metabolizing enzymes in human prostate with a high interindividual variability may be involved in the regulation of local levels of carcinogens and mutagens and may underie interindividual differences in cancer susceptibility. 1362 JAG Agundez et al due to a strong local effect on the actixation or deactivation of carcinogens in situ. For instance. it has been shovA-n that N-acetvltransferase polx morphism play s a relevant role in the formation of 2-aminofluorene-DNA adducts in tumour target organs (Feng et al. 1996). In an attempt to elucidate the events that occur as previous steps to prostate carcinogenesis. x e hax e studied A hether the poix-morphic enzymes CYP2D6 and NAT2 are actix ely expressed in human prostate tissue. as well as the impact of such genetic polx morphisms in prostate cancer susceptibility. In order to ex aluate w-hether allelic loss of these genes occurs in adenomatous prostate tissue. the occurrence of allelic losses at the CYP2D and .VA72 gene loci in prostate tissues was also studied. If the CYP2D6 enzyrme is functionally expressed in prostate. allelic loss of CYP2D6 could cause changes in local enzyme activity. modifving the local metabolism of carcinooens and mutarens. To our know-ledge. no studies involving allelic loss of the polymorphic gene CYP2D6 haxe been performed. This is also the first study inxolxing allelic loss of the NVA72 gene in prostate. Indeed only one study involvin2 allelic loss of NAT2 has been published. and it was performed in colon cancer (Hubbard et al. 1997). Keywords METHODS Patients and controlsAll the subjects included in this studx were unrelated v hite Spanish men. samples from t...

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Background/Aims: Autosomal dominant Alport syndrome represents 5% of all Alport syndrome cases. This entity presents a different clinical expression from the recessive inheritance pattern and the X chromosome-linked pattern, because it is mild and it shows a late onset, which in many cases even goes unnoticed. Methods: We carried out a descriptive observational and retrospective clinical study on 19 patients from 5 families with a clinical diagnosis of autosomal dominant Alport Syndrome, and we analyzed the expression of the symptoms in the different families, comparing the results with what has been described in the literature. Results: Renal involvement appeared at a young age, with a progression towards end-stage chronic kidney disease at a median age of 31 years (20.5-36.5). Hearing involvement also appeared in early stages, at a median age of 28.5 years (7.5-62.5). Also, we observed ocular lenticonus-like injuries, which until now have only been described in other inheritance patterns. Conclusions: Our results suggest that dominant patterns are accompanied by a severe clinical expression that can be superimposed to the recessive and X chromosome-linked patterns, contrary to what has been classically stated. The high phenotypic variability observed in the families lead to the fact that many cases go unnoticed and the severest cases are erroneously diagnosed as recessive, which means that the real prevalence of dominant forms is probably higher than the current 5%.

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Tuberous sclerosis is rarely associated with autosomal dominant polycystic kidney disease in the so-called tuberous sclerosis complex. This association leads to an increased frequency of end-stage renal disease. We present a patient suffering from both syndromes, who received a renal graft and anticalcineurinic drugs as immunosuppressive agents. Progressive titration of the drug was necessary in order to attain the effective doses due to the enzymatic induction caused by concomitant treatment with antiepileptic drugs. These high doses resulted in nephrotoxicity. Immunosuppressor treatment was switched to rapamycin, whereby an improvement in renal function and other signs of tuberous sclerosis and polycystic kidney disease was observed. This case report highlights both the efficacy and safety of rapamycin as an immunosuppressor treatment and its capacity for controlling other symptoms of these genetic-related disorders.

Lanthanum carbonate is a nonaluminum, noncalcium phosphate-binding agent, which is widely used in patients with end-stage chronic kidney disease. Until now, no significant side-effects have been described for the clinical use of lanthanum carbonate, and there are no available clinical data regarding its tissue stores.Here we report the case of a 59-year-old patient who was admitted with confusional syndrome. The patient received 3750 mg of lanthanum carbonate daily. Examinations were carried out, and the etiology of the encephalopathy of the patient could not be singled out. The lanthanum carbonate levels in serum and cerebrospinal fluid were high, and the syndrome eased after the drug was removed. The results of our study confirm that, in our case, the lanthanum carbonate did cross the blood-brain barrier (BBB).Although lanthanum carbonate seems a safe drug with minimal absorption, this work reveals the problem derived from the increase of serum levels of lanthanum carbonate, and the possibility that it may cross the BBB. Further research is required on the possible pathologies that increase serum levels of lanthanum carbonate, as well as the risks and side-effects derived from its absorption.

Background and Aims Primary aldosteronism is a rare cause of high blood pressure (BP). Guidelines recommend a screening in several situations, such as hypertension with hypokalemia, sleeping apnea or adrenal mass, by determining the baseline aldosterone/renin ratio. Recent studies point out that hyperaldosteronism may be more frequent than expected in patients who do not have an arbitrary high aldosterone/renin ratio. The application of big data techniques could generate “red flags” that help clinicians to anticipate the diagnosis. We have evaluated the usefulness of big data in the diagnosis of hyperaldosteronism. Method We have used 3 data sources: patient management, laboratory data management and clinical record. With them, Oracle database management system extracts demographic data, blood pressure and analytical values in a single collection. This data are stored in a MongoDB database, where two collections are generated: "patients" (data we are collecting) and "variables" (values obtained from the identifiers of the latest data obtained from the source systems are saved to guide the collection process). Since MongoDB is a schemaless system, it is possible to easily add new variables and their results to the collection "patients", if it is necessary, in order to generate alerts. In order to diagnose hyperaldosteronism, age between 18 and 55 years, BP > 139/89 mmHg, K 3.5 mEq/l and plasma bicarbonate > 26 mEq/L were used. Results From January 2019 to 30th March 2020, 952,520 data were collected and 281,661 outcome variables from 80,410 patients were analyzed. The method generated alerts of possible hyperaldosteronism in 33 patients (18 men, mean age 46.8 + 6.8 years old). The retrospective study of the clinical record of these patients showed that 11 (33%) had sustained hypertension and 54.5% of them needed 3 antihypertensive drugs. 2 patients suffered a severe cardiovascular event (intracranial hemorrhage). Of these 33 patients, aldosterone/renin screening was performed in 2, 2 other patients had an abdominal CT scan, in which no adrenal masses were found. No specific studies were performed to definitively rule out hyperaldosteronism in any patient. In this period of application of big data, the hospital archive coded 3 hyperaldosteronisms: 1 of them was due to Bartter syndrome, another was a misdiagnosis (androgenic syndrome) and the third one was due to medical background of hyperaldosteronism which had been operated years ago. These results were followed by a prospective screening carried on from 30th March 2020 to 1th January 2021. 776,878 supplementary data were extracted, and 232,425 variables from 13,958 patients were analyzed. The system have generated an alert for 12 patients: 2 of them have been diagnosed of primary hyperaldosteronism, another one have an adrenal mass, which is in surgical waiting list, and 3 patients (total: 50%) are waiting medical tests due to a high suspicion of hyperaldosteronism. Conclusion Big data techniques allow us to create “red flags” for the screening of rare diseases and might be an important tool in their diagnosis. Its systematic application guides us to perform specific diagnostic tests in at least 50% of the cases, in order to improve the diagnostic accuracy in these selected patients.

Cardiorenal syndrome is a severe and potentially lethal disease in which heart and kidney failures coexist. The classic treatment with loop diuretics is ineffective due to the resistance of the kidney to those drugs, which requires the use of other therapies, such as extracorporeal ultrafiltration and peritoneal dialysis. This last technique is useful both in the acute treatment of acute heart decompensation and the chronic management of heart failure, because it improves heart function by reducing the volume overload, which in turn contributes to improving the kidney function with a limited number of side effects, which makes it the technique of choice for the treatment of diuretic-resistant heart failure. In this review, we present a description of the different kinds of cardiorenal syndrome, as well as the different treatments that are used, with special attention to the different modalities of peritoneal dialysis.