Progression of secondary hyperparathyroidism involves deregulation of genes related to DNA and RNA stability.

BACKGROUND: Renal secondary hyperparathyroidism in its late stages becomes autonomous, so excessive parathyroid hormone (PTH) secretion no longer responds to physiologic stimuli or to aggressive medical treatment. METHODS: To gain molecular understanding of progression of renal secondary hyperparathyroidism, normal and hyperplastic parathyroid tissue with diffuse and nodular growth were analyzed. The results were also compared to parathyroid adenomas. The analysis was performed by high-density oligonucleotide microarray and bidirectional subtraction library. RESULTS: Analysis of the DNA arrays found 16 overexpressed and 132 repressed genes in the nodules while the subtraction library produced 34 overexpressed and 40 repressed genes. The differentially expressed genes between diffuse and nodular samples included some related to DNA stability and repair (TALDO1, PRDX2, DDB1, XRCC1, and POLB), RNA stability and degradation (OASL and AUF1), protein synthesis and processing (PFDN5, HSPD1, and NACA), cell growth (CDC25C and GRPR), and tumorigenesis and cell cycle (VIL2 and TPD52). CONCLUSION: According to the function described for the deregulated genes, when secondary hyperparathyroidism becomes autonomous and refractory to treatment, RNA degradation may be increased while DNA integrity may be compromised. These two mechanisms, combined with deregulation of genes related to growth and differentiation show the complex pathway of parathyroid glands' evolution in renal hyperparathyroidism and may explain the large amount of molecular cytogenetic aberrations found in refractory hyperparathyroidism. Considering that some of the genes with altered expression in nodular hyperplasia lead to irreversible consequences in the genomic integrity of the cells, an adequate and early management of the secondary hyperparathyroidism of chronic kidney disease becomes mandatory.

Parathyroidectomy: whom and when?

Hyperparathyroidism (HPT) is common in patients on dialysis, and parathyroidectomy (PTx) is often required. We present a retrospective, descriptive analysis of data corresponding to 148 patients on dialysis undergoing PTx due to severe refractory HPT (PTH 1401 +/- 497 pg/mL, Ca 10.6 +/- 0.8 mg/dL, P 6.9 +/- 1.7 mg/dL). Demographic data were compared with those recorded in 309 patients on dialysis not subjected to PTx who were managed at the same hospital. In the PTx group, the factors age (49.3 +/- 14 years), male gender (48.6%), and diabetes (0.7%) were significantly lower than in the non-PTx group (61.5 +/- 14.9 years, male gender 59%, diabetes 19.4%), while time on dialysis was longer (8.6 +/- 5.8 vs. 5.5 +/- 5.4 years). In 129 of the study patients (87.4%), four or more glands were identified, and total PTx plus autotransplantation (AT) in the forearm was performed. In the remaining 19 patients, two to three glands were identified, and AT was not undertaken. Four of the 19 patients were successfully operated on again for persistent HPT, seven showed PTH levels <250 pg/mL, and eight maintained severe HPT. Perioperative complications included one death due to cardiac insufficiency, two repeat operations due to bleeding, and one patient with chronic hoarseness. Hospital stay was prolonged in 20% of patients due to a hungry bone syndrome. Among those patients with PTx and AT, HPT recurred in 21 patients (16.2%) at 3.1 +/- 2.3 years. In 13 of these patients, autograft was removed at 7.5 +/- 2.9 years. Serum calcium and phosphate levels improved after PTx, and these results were maintained for 5 years (9.6 +/- 0.8 and 4.2 +/- 1.2 mg/dL, respectively). In conclusion, PTx with AT is a safe option for the treatment of severe HPT that is accompanied by low morbidity and mortality and a good outcome. Medical treatment should not be prolonged at the expense of long repeated bouts of hypercalcemia and/or hyperphosphatemia with their irreversible consequences.

Chromosomal imbalances identified by comparative genomic hybridization in sporadic parathyroid adenomas.

OBJECTIVE: To identify chromosomal gains and losses in sporadic parathyroid adenomas (PAs). METHODS: Fourteen sporadic PAs were studied by comparative genomic hybridization (CGH). RESULTS: The fourteen studied PAs showed chromosomal imbalances. All cases except one exhibited two or more abnormalities. Chromosomal gains were found in all cases, and three cases (21%) also presented chromosomal losses. Genomic amplification was not observed. Chromosome 9 was involved in ten cases. Recurrent genetic gain was found on 9p22-24 and on 9q34, each in 6 of 14 cases (43%). Other recurrent gains included Xq26 in 6 PAs (43%) and 4q21-28 and 8p22-23, each in 4 of 14 cases (29%). Regions of recurrent genetic loss involved whole chromosome 11 and 20q12-13, each in 2 of 14 cases (14%). CONCLUSIONS: Our findings show chromosomal imbalances in all sporadic PAs studied by CGH, partly confirming previous reports, with the exception that we observed more chromosomal gains than losses. Several regions (9p22-24, 9q34, Xq26, 4q21-28, and 8p22-23) probably deserve further investigation in order to discard the presence of genes involved in parathyroid tumorigenesis.

Aspergilosis de la herida en trasplantes hepáticos / Aspergillosis of the wound in liver transplantation

La aspergilosis cutánea se asocia, generalmente, a inmunosupresión, quemaduras o traumatismos severos. La mayoría de los casos son adquiridos por inoculación directa, aunque ocasionalmente, el compromiso cutáneo es secundario a una enfermedad diseminada. Hasta el momento no existen comunicaciones de infecciones de la herida quirúrgica causadas por Aspergillus. En este trabajo describimos dos pacientes trasplantados hepáticos, los cuales desarrollan aspergilosis de la herida quirúrgica, durante un brote de aspergilosis relacionado con la renovación del Hospital. La infección se desarrolló en el postoperatorio inmediato y simuló en apariencia una fascitis necrotizante. Ambos pacientes murieron a pesar del debridamiento local y del tratamiento con anfotericina B. Debe adicionarse el Aspergillus a la lista de posibles agentes que pueden infectar las heridas quirúrgicas, especialemente en los casos de trasplantes de órganos.