Multifocal renal allograft biopsy: impact on therapeutic decisions.

OBJECTIVE: There are no data to support the suggestion that samples removed from one segment of the transplanted kidney are representative of the whole graft. The aim of this study was to compare the histological differences between biopsies obtained from different portions of the renal allograft and their impact on treatment recommendations. PATIENTS AND METHODS: Two hundred percutaneous biopsies were performed on kidney allografts and samples were collected from the upper and lower poles (100 kidneys). All samples were randomized and blindly reviewed. We obtained the discordance rates between the poles for the grading of acute rejection and for the diagnosis of nephrotoxicity due to immunosuppression. We also checked if the differences found were sufficient to call for different clinical recommendations. These values were compared with the intrapathologist variation rates. RESULTS: In 70 kidneys adequate sampling was obtained from both poles. The diagnosis of acute rejection were made in 17. The discordance rate between the upper and lower poles was 82.3% (kappa = 0.34), higher than the intrapathologist variation (P = .002). Nephrotoxicity was found in 14 kidneys. The discordance rate between the upper and lower poles was 28.6% (kappa = 0.88), with no difference compared with the intrapathologist variation. In 14 of the 70 kidneys (25.7%), discordances between poles had impact on clinical recommendations, most of these cases due to different gradings of acute rejection (78%). This number was higher than the intrapathologist variation (P = .04). CONCLUSIONS: The histopathological changes in the kidney allograft are not always homogeneous. This heterogeneity may affect the therapeutic recommendations.

Ectopic ACTH syndrome caused by pheochromocytoma: computed tomography-guided percutaneous ethanol injection as an alternative treatment.

Ectopic ACTH secretion represents 8-18% of the cases of endogenous hypercortisolism. Pheochromocytomas correspond to 2-25% of the cases and surgery is the indicated treatment. We describe a case of ACTH-secreting pheochromocytoma treated with percutaneous ethanol injection (PEI) guided by computed tomography (CT). A 71-yr-old man presented with diabetes, severe hypokalemia, weight loss, muscle weakness, and hypertension. Hormonal evaluation revealed elevated levels of urinary cortisol, ACTH, catecholamines, and urinary metanephrines. There was no cortisol or ACTH response to desmopressin stimulation test. Magnetic resonance revealed bilateral adrenal nodules, larger on the left side. The suspected diagnosis was ectopic ACTH syndrome caused by pheochromocytoma. Ketoconazole treatment resulted in reduction of urinary cortisol levels but was followed by severe cholestasis and hepatic dysfunction, preventing surgery; it was substituted by octreotide with reduction of ACTH and cortisol levels, but without improvement of cholestasis. The patient presented cachexia and developed multiple pulmonary abscesses that also prevented surgical treatment, thus he was treated with percutaneous ethanol injection guided by CT of the left adrenal tumor. During the procedure, the patient had an increase in blood pressure controlled by the infusion of sodium nitroprusside followed by hypotension that required infusion of dopamine and volume expansion. Afterwards, he presented hormonal normalization, normal catecholamines levels, and clinical improvement. Histological tissue analysis confirmed pheochromocytoma. We concluded that CT-guided PEI represents an efficient alternative therapy to ectopic ACTH-secreting pheochromocytomas in patients without clinical conditions for surgery.

An inherited mutation outside the highly conserved DNA-binding domain of the p53 tumor suppressor protein in children and adults with sporadic adrenocortical tumors.

Mutations of the p53 tumor suppressor gene are the single most common genetic alterations in human cancers. Recently, a distinct nucleotide substitution was identified in exon 10 of the p53 gene, leading to an Arg337His mutation in 97% of children with adrenocortical tumors from Southern Brazil. In the present study, we investigated the presence of this mutation in a larger series of 55 patients (37 adults and 18 children) with benign and malignant sporadic adrenocortical tumors. None of the patients had family cancer histories that conformed to the criteria for Li-Fraumeni syndrome. Twenty-one asymptomatic close relatives of patients with p53 mutations and 60 normal unrelated individuals were also studied. The missense Arg337His mutation was identified in 19 patients (14 children and 5 adults), and 8 of 11 cases studied had LOH. Among the 19 patients with the Arg337His mutation, only one boy and three adults showed fatal evolution or recurrent metastases. This mutation was also identified in heterozygous state in asymptomatic first-degree relatives of the patients, indicating that Arg337His mutation was inherited in most cases. In contrast, this mutation was not found in 120 alleles of normal unrelated controls. In conclusion, the germ line Arg337His mutation of p53 protein is present at a high frequency (77.7%) in children with benign or malignant sporadic adrenocortical tumors, but it is not restricted to the pediatric group, since 13.5% of adults with adrenocortical tumors also had this mutation. The presence of this mutation was related to unfavorable prognosis in most of the adults, but not in the children with adrenocortical tumors.

Growth hormone receptor messenger ribonucleic acid in normal and pathologic human adrenocortical tissues--an analysis by quantitative polymerase chain reaction technique.

GH receptor (GHR) has been reported to express in both normal rat and human adrenals. However, no study examined GHR expression in diseased human adrenal cortex. We quantitated, with RT-PCR, GHR messenger RNA (mRNA) in both normal and diseased human adrenal cortex with the following results: GHR mRNA levels in four histologically normal, not steroid-stimulated, control adrenal cortices was 1.5-11 x 10(4) molecules/microgram total RNA; in three diffusely hyperplastic adrenals (DH): 6.7-17.7 x 10(4); in two nonfunctioning tumors (NF): 0.84-1.9 x 10(4); in five androgen-producing neoplasms (AP): 4.6-34 x 10(4); and in five glucocorticoid-producing neoplasms (GP): 6.7-87 x 10(4). GHR transcript levels among adrenal cortices, DH, NF, AP, and GP reached statistically significant difference (P < 0.03). The GP group exhibited higher GHR mRNA levels than controls (P < 0.006). NF, as well as GP and AP, tumors had less GHR mRNA than their histologically normal adjacent cortex (P < 0.05). A positive correlation between urinary cortisol and GHR messenger RNA (mRNA) levels from GP and DH was observed (r = 0.93, P < 0.003). Our data suggest that GHR is expressed in both normal and diseased adrenal cortex and that GHR mRNA accumulation is less efficient in adrenocortical neoplasm than their adjacent nonneoplastic cortex. GHR expression in adrenal cortex provides an evidence of direct GH action in this tissue.

Histological outcome of acute cellular rejection in kidney transplantation after treatment with methylprednisolone.

BACKGROUND: Several studies comparing the response of acute cellular rejection (ACR) episodes to different corticosteroid regimens have been conducted. However, in most of them, the histological evaluation of the infiltrate and its correlation with clinical response was not studied. The clinical and histological outcomes of 37 episodes of ACR treated with methylprednisolone (MP) were studied, with the aim to determine how long the infiltrate takes to be cleared after therapy. METHODS: A total of 37 patients with biopsy-proven ACR were treated with 8 or 16 mg of MP/kg/day. Allograft biopsies were repeated at 5 and 10 days after the end of corticotherapy. Clinical and histological outcomes were compared. RESULTS: Six patients were excluded; 15 (48.4%) patients responded to therapy; the mean serum creatinine of these patients reached normal levels in the 2 weeks that followed treatment. Nine patients (60%) of this group had signs of ACR on biopsies done 5 days after corticotherapy, and four (26.7%) maintained them on the 10th day. Among 16 patients with no clinical response, none reached normal serum creatinine levels; 15 (93.7%) had signs of rejection 5 days after treatment and maintained them on the 10th day. Histological signs of ACR disappeared in 73.3% of patients with clinical response 10 days after therapy, but in only 6.3% of patients with no response (P=0.001). CONCLUSIONS: Biopsies performed 5 days after treatment show a high incidence of features of ACR; such features take on average 10 days to disappear in nearly 75% of cases with successful therapy with MP.

Veno-occlusive dysfunction of corpora cavernosa: comparison of diagnostic methods.

Pump cavernosometry, pharmaco-cavernosometry, gravity cavernosometry and the intracavernous pressure drop test are the most used tests for the diagnosis of venoocclusive dysfunction. To verify whether patients show equivalent results in each of these four tests, and to ascertain whether there is any influence of the sequence of the exams over the results, 123 male patients with erectile dysfunction, aged 21 to 82 years (mean 48), were evaluated. All were submitted to the four tests in randomized sequence. Two criteria were used to define the normal results of pump cavernosometry and pharmaco-cavernosometry, both based on patients with normal veno-occlusive function. The incidence of normal results varied from 6.5% in pump cavernosometry according to criterion I to 64.2% in pharmaco-cavernosometry according to criterion II. Results of the four tests agreed completely (all normal or all abnormal) in 43.9% of the patients when criteria I was used and 58.3% with criteria II. Incidence of normal results in each test did not vary according to the sequence in which the exams were done. Pump cavernosometry, pharmaco-cavernosometry, gravity cavernosometry and intracavernous pressure drop test did not show equivalent results for individual patients. Results were not influenced by the sequence of the tests.

Urethroplasty using a bovine pericardium graft: an experimental study using normal urethras from dogs.

The use of bovine pericardium as a urethral patch to substitute a ventral segment of canine urethras was studied. Healing, epithelial growth, urethral permeability, fistulas, and calcification were analyzed. Thirty male mongrel dogs of medium and large size underwent resection of a ventral segment of the medial urethra measuring 2.0 x 0.5 cm, which was replaced with a bovine pericardium graft, treated with buffered glutaraldehyde and preserved in formaldehyde. Two running sutures of polygalactin 5-0 were applied, one on each side of the patch. The corpus spongiosum was closed with uninterrupted suture and the skin with interrupted suture of polygalactin 5-0. Six months later, the animals were examined and sacrificed under anesthesia. Retrograde urethrograms showed that the urethral healing was complete in six of the 30 animals, without stenosis, fistulas or dilations. Microscopic examination showed complete epithelization of these six urethras. The remaining 24 animals presented urethrocutaneous fistulas without stenosis, demonstrated by urethral catheterism using a 10-Fr plastic catheter. These data show that a successful urethral reconstruction of the penile urethra was possible in only 20% of the operated animals. Infection and leakage may be the cause of the urethrocutaneous fistulas present in 80% of cases. Further studies are necessary to determine whether such fistulas are avoidable. If they are, the bovine pericardium may well be an option in the treatment of urethral lesions in dogs.

HPV prevalence among partners of women with cervical intraepithelial neoplasia.

OBJECTIVES: The objective of this study was to find HPV DNA incidence in women with CIN and normal women and in their respective partners, as well as the relation between the virus groups found in women with CIN or normal women and in their respective partners. METHODS: Partners of 30 women with CIN at several grades and of 60 normal women were prospectively assessed. In men, HPV search was performed by collecting samples through penile scraping for Hybrid Capture, followed by peniscopic evaluation and biopsy of acetowhite lesions. RESULTS: The presence of HPV DNA in male partners does not necessarily implicate the presence of HPV or even CIN in their female partners. CONCLUSIONS: If these results are confirmed by other authors, obtaining a peniscopy, a penile biopsy, and a HPV DNA search in partners that present with no clinical lesions, but in couples with women having CIN, would not be warranted.

Vesical haemangioma. Report of two cases.

Two cases of vesical haemangioma and a review of the literature are presented. In one of the cases association with cutaneous "Blue Rubber Bleb Nevus" has been found. Vesical haemangioma is a benign tumour, probably of congenital origin, that occurs in young patients. The first symptom is generally haematuria, and diagnosis is confirmed by cystoscopy. The treatment of choice is partial cystectomy, and the most common histologic form is cavernous haemangioma.

[Assessment of erectile dysfunction in patients with Parkinson's disease]. / Avaliação da disfunção erétil em pacientes com doença de Parkinson.

Thirty men having Parkinsons disease (PD) and 30 controls were studied prospectively by the use of the International Index of Erectile Function (IIEF) to assess erectile dysfunction (ED). Of the patients with PD (mean age of 59 years), 46.66% referred to the practice of sexual activity. All of the parkinsonians were using antiparkinsonian medication. In the control group (mean age of 63 years), 76.66% referred to the practice of sexual activity, 46.60% to arterial hypertension and 6.66% to diabetes mellitus. The median score for the PD group according to the IIEF was 34, and that for the controls 50. The main differences between the two groups were in the erectile function, orgasmic function and satisfaction with the sexual relationship. The IIEF is a multidimensional scale widely accepted to assess the ED. The data obtained suggest that ED is more frequent among parkinsonians and points out to the role of DP in the genesis of ED.

Catheter-associated urinary infection in kidney post-transplant patients.

CONTEXT: There is still controversy as to the use and dosage of antimicrobial prophylaxis of the urinary infection associated with urethral catheterization in the post renal transplant period. OBJECTIVE: To determine whether patients develop urinary infection during short-term urethral catheterization after renal transplant without routine antimicrobial prophylaxis. DESIGN: Prospective study. SETTING: Kidney Transplantation Unit. SAMPLE: 20 patients submitted to non-complicated kidney transplant, with a normal urinary tract and no risk factors present regarding urinary infection. Aged 15 to 65 years. MAIN MEASUREMENTS: Before the transplant, material from the urethral meatus and urine were collected for culture. After the transplant, in the period during which the patient was with short-term urethral catheterization (4 to 5 days), material from the urethral meatus and urine from the bladder and the collecting bag were taken daily from all recipients for culture. RESULTS: There was a predominance of coagulase-negative Staphylococcus and S. viridans in the normal urethral meatus flora and in the first two days of urethral catheterization. After the second day, there was a predominance of E. coli and E. faecalis. Urinary infection did not occur during the period of urethral catheterization. In the follow up only one female patient (7%) had asymptomatic bacteriuria caused by E.coli after the withdrawal of the urethral catheter. CONCLUSIONS: Infection urinary does not occur during the period of urethral catheterization in kidney post-transplant patients. Thus, antimicrobial prophylaxis is not recommended for these patients to prevent urinary infection.

Multicentric pheochromocytoma and involvement of the inferior vena cava.

CONTEXT: Extension of pheochromocytomas to the inferior vena cava is rare. Multicentric tumors are rare as well, being present in up to 10% of cases. Surgery is the treatment of choice because of the long-term survival free of disease. DESIGN: Case report. CASE REPORT: We report on a case of right adrenal pheochromocytoma with extension to the supra-diaphragmatic vena cava, which underwent surgical excision through thoracophrenic laparotomy without the need for cardiopulmonary bypass. In a 6-year follow-up, another pheochromocytoma was found in the infra-renal Zuckerkandl's organ. Complete surgical excision of the tumor was performed by a median laparotomy and complete retroperitoneal dissection. In both cases, the total removal of the pheochromocytoma has been guaranteed by having margins free of tumor and a normal post-operative level of catecholamines. The pathological study revealed a malignant pheochromocytoma with margins free of neoplasia in both specimens.

[Percutaneous angioplasty and surgical revascularization in renovascular hypertension: experience in treatment and long-term follow up in 124 patients]. / Angioplastia percutânea e revascularização cirúrgica em hipertensão renovascular. Experiência no tratamento e seguimento de longo prazo em 124 pacientes.

PURPOSE: To report the experience in the treatment and long-term follow-up of patients with renovascular hypertension submitted to angioplasty and/or surgical revascularization, and to compare blood pressure and renal function responses to both treatment. METHODS: One hundred and twenty-four patients diagnosed with renovascular hypertension, divided, according to the etiology, as atherosclerosis (76 patients), fibromuscular dysplasia (32) and arteritis (16), were submitted to isolated or associated treatment of renal revascularization by percutaneous transluminal angioplasty (71 patients) or surgery (84). The patients were followed-up during 2.5 +/- 1.5 years and we evaluate blood pressure response and renal function preservation. In relation to blood pressure control, the patients were considered as cured when normotensives without antihypertensives, improved when normotensives with fewer drugs than previously, and unchanged, when out of these criteria. RESULTS: From 124 patients, 20% were considered cured, 54% improved and 26% unchanged, after a mean follow-up of 2.5 +/- 1.5 years. Patients with atherosclerosis and fibromuscular dysplasia presented a higher rate of care and improvement after surgery. The blood pressure and the number of antihypertensive drugs decreased significantly during the follow-up among patients that cured or improved arterial hypertension, either after angioplasty (190 +/- 26/115 +/- 14 mmHg vs 130 +/- 34/85 +/- 7 mmHg. 2.70 vs 1.60 drugs) or after surgery (194 +/- 17/115 +/- 16 mmHg vs 143 +/- 18 mmHg vs 88 +/- 8 mmHg, 1.88 vs 1.51 drugs). It was also observed a significant decrease of serum creatinine among these patients. CONCLUSION: Renal revascularization in patients with renovascular hypertension, either by angioplasty or surgery, is beneficial to control blood pressure and to preserve renal function in the majority of patients.

Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation.

We investigated the effects of the antioxidant N-acetylcysteine (NAC) on early outcomes of deceased donor renal transplantation. Between April 2005 and June 2008, adult primary graft recipients of deceased renal donors were assigned to treatment (n = 38) or control (n = 36) groups and evaluated for 90 days and one year after renal transplantation. The treatment group received NAC orally (600 mg twice daily) from day 0 to 7 postoperatively. Renal function was determined by serum creatinine, MDRD and Cockcroft-Gault estimated GFR (eGFR), delayed graft function (DGF) and dialysis free Kaplan-Meier estimate curve. Serum levels of thiobarbituric acid reactive substances (TBARS), were employed as markers of oxidative stress. The NAC group displayed a lower mean serum creatinine during the first 90 days (P = .026) and at 1 year after transplantation (P = .005). Furthermore, the NAC group showed a higher mean eGFR throughout the first 90 days and at 1 year. DGF was lower among the NAC group (P = .017) and these recipients required fewer days of dialysis (P = .012). Oxidative stress was significantly attenuated with NAC (P < .001). Our results suggested that NAC enhanced early outcomes of deceased donor renal transplantation by attenuating oxidative stress.

Hemorrhagic cystitis secondary to adenovirus or herpes simplex virus infection following renal transplantation: four case reports.

Viral infections are common complications following renal transplantation. However, there have been few reported cases of viral cystitis secondary to herpes simplex virus or adenovirus infection. Herein, we have reported four cases of hemorrhagic cystitis secondary to infections with herpes simplex virus and adenovirus following renal transplantation. The etiology was adenovirus in three cases and herpes simplex virus in the remaining case. In all four cases, the primary cause of the renal dysfunction was diabetic nephropathy. All four patients presented with a clinical profile characterized by dysuria, pollakiuria, macroscopic hematuria, and graft dysfunction. Three of the four patients developed these symptoms within the first 3 months after renal transplantation. In all four cases, there was an increase, albeit slight, in creatinine levels, which returned to normal or near-normal values upon resolution of the symptoms. Acute cellular rejection was observed in only one case. Although rare, hemorrhagic cystitis secondary to infection, which typically occurs early in the posttransplant period, causes pronounced symptoms. The infection appears to be self-limiting, resolving completely within 4 weeks.

Renal autotransplantation in the treatment of hypertensive disease associated with unilateral renal artery stenosis.

Renal autotransplantation was performed on 15 subjects with renovascular hypertensive disease owing to unilateral renal artery stenosis. Kidney survival was achieved in 14 cases. Followup for a minimum of 6 months showed 50 per cent of the patients to be cured, 28 per cent improved and 22 per cent unchanged according to the criteria described herein. There was an 85 per cent cure rate among a subgroup of patients less than 35 years old, with less than 20 months of hypertension and non-atherosclerotic lesions. Plasma renin assay was not found to be a good prognostic indicator as reported previously. In our hands the method showed only a 70 per cent correlation with the final results. Non-atherosclerotic lesions had a better prognosis.