Malignant fibrous histiocytoma of perirenal tissue: a case report

A 75-year-old woman was admitted to our hospital with an extremely large retroperitoneal tumor that had been detected with ultrasound on a routine health check. She had no complaint except lumbar pain. Computed tomography revealed a heterogenous tumor located outside the right kidney which was enhanced gradually. Doppler ultrasound showed mild vascularity in the tumor. We performed tumorectomy and right nephrectomy because the tumor was adherent to the right kidney. The tumor was 16 x 11 x 7 cm in size and weighed 621 g. The histopathological diagnosis was malignant fibrous histiocytoma. The tumor was considered to have arisen from perirenal tissue.     

Dietary l-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

Vascular calcification (VC) is a life-threatening complication of CKD. Severe protein restriction causes a shortage of essential amino acids, and exacerbates VC in rats. Therefore, we investigated the effects of dietary l-lysine, the first-limiting amino acid of cereal grains, on VC. Male Sprague-Dawley rats at age 13 weeks were divided randomly into four groups: low-protein (LP) diet (group LP), LP diet+adenine (group Ade), LP diet+adenine+glycine (group Gly) as a control amino acid group, and LP diet+adenine+l-lysine·HCl (group Lys). At age 18 weeks, group LP had no VC, whereas groups Ade and Gly had comparable levels of severe VC. l-Lysine supplementation almost completely ameliorated VC. Physical parameters and serum creatinine, urea nitrogen, and phosphate did not differ among groups Ade, Gly, and Lys. Notably, serum calcium in group Lys was slightly but significantly higher than in groups Ade and Gly. Dietary l-lysine strongly suppressed plasma intact parathyroid hormone in adenine rats and supported a proper bone-vascular axis. The conserved orientation of the femoral apatite in group Lys also evidenced the bone-protective effects of l-lysine. Dietary l-lysine elevated plasma alanine, proline, arginine, and homoarginine but not lysine. Analyses in vitro demonstrated that alanine and proline inhibit apoptosis of cultured vascular smooth muscle cells, and that arginine and homoarginine attenuate mineral precipitations in a supersaturated calcium/phosphate solution. In conclusion, dietary supplementation of l-lysine ameliorated VC by modifying key pathways that exacerbate VC.Medial vascular calcification is common in aging, diabetes, and CKD.^1–4 Because the presence of vascular calcification is strongly associated with increased cardiovascular morbidity and mortality, several studies in both animals and humans have sought ways to reduce the extent of vascular calcification.^5–10 However, satisfactory therapies have not yet been established.¹¹Adenine-induced renal failure is one of the commonly used animal models for studying the development of vascular calcification, but the prevalence of vascular calcification in this model is not very high. Indeed, Price et al. reported that vascular calcification was detected in only 30% of rats with adenine-induced chronic renal failure (adenine rats) fed a normal-protein diet.⁵ These authors speculated that consistent vascular calcification might require a longer period of adenine feeding. On the basis of this idea, they designed a low-protein (LP) diet in an attempt to reduce the nitrogen load and thus enable the rats to thrive on the adenine diet for longer periods. As a result of this attempt, Price et al. unexpectedly found that adenine rats fed a LP diet had extensive vascular calcification without a longer feeding period.⁵ All 13 adenine rats fed the LP diet had uniform alizarin red staining of the aorta, whereas only 3 of the 11 adenine rats fed a normal-protein diet had partial calcification.⁵ These findings indicated that dietary protein deficiency correlates with the extent of vascular calcification.Proteins are usually made from 20 kinds of amino acids. On the basis of nutritional requirements, these amino acids can be divided into two groups: essential amino acids (EAAs) and non-EAAs. Because restriction of dietary protein results in a shortage of EAAs, the level of dietary EAAs may be relevant to the extent of vascular calcification. Among nine EAAs, this study focused on l-lysine (l-Lys) based on the following three reasons. First, l-Lys is the first-limiting amino acid in most cereal grains.¹² Second, the safety of l-Lys supplementation has been verified in the area of animal husbandry. l-Lys has long been added to feed grains in order to improve the utility of feed proteins.¹³ Third, several studies have demonstrated that dietary supplementation with l-Lys protects bones from osteoporosis, a pathologic condition that often coexists with vascular calcification.^14,15 These points prompted us to hypothesize that supplementation with l-Lys would ameliorate vascular calcification. Therefore, in this study, we tested this hypothesis using adenine rats.     

Diagnosis of vasospastic angina by analysis of heart rate response to exercise: effects of different levels of work load

To examine alterations in control functions of the heart, which may account for the pathophysiologic conditions precipitating coronary arterial spasm, heart rate response to exercise in vasospastic angina was evaluated by using our previously developed method of frequency analysis. We also examined the effects of three different levels of work load on the heart rate response to treadmill exercise in 9 patients with vasospastic angina and 7 normal controls: stage 1 (2.5 Km/h, 10%), stage 3 (4.5 Km/h, 10%), and stage 5 (5.5 Km/h, 14%). The transfer function of heart rate control in vasospastic angina was characteristically different from that in normal controls: lower gain and more delayed phase angle of the system. Although this abnormality was observed in every test at 3 different levels of work load, the abnormality was more striking in tests at lower levels of work load: stage 1 or 3. The moderately light exercise test at stage 3 is most suitable as a test for detecting abnormal heart rate response to exercise in vasospastic angina because the exercise test at stage 1 had a poor S/N ratio.     

Laparoscopic transabdominal preperitoneal inguinal hernia repair using needlescopic instruments: a 15-year, single-center experience in 317 patients

Background

Laparoscopic inguinal hernia repair is associated with a decrease in postoperative pain, shortened hospital stay, earlier return to normal activity, and decrease in chronic pain. Moreover, laparoscopic surgery performed with needlescopic instruments has more advantages than conventional laparoscopic surgery. However, there are few reports of large-scale laparoscopic transabdominal preperitoneal inguinal hernia repair using needlescopic instruments (nTAPP). This report reviews our experiences with 352 nTAPP in 317 patients during the 15-year period from April 1996 to April 2011.

Methods

We performed nTAPP as the method of choice in 88.5% of all patients presenting with inguinal hernia. To perform the nTAPP, 3-mm instruments were used. A 5-mm laparoscope was inserted from the umbilicus, and surgical instruments were inserted through 5- and 3-mm trocars. After reduction of the hernia sac and dissection of the preperitoneal space, we placed polyester mesh or polypropylene soft mesh with staple fixation. The peritoneum was closed with 3–0 silk interrupted sutures.

Results

The mean operative time was 102.9?min for unilateral hernias and 155.8?min for bilateral hernias. There was no conversion to open repair. Forty-three patients (13.6%) used postoperative analgesics, and the mean frequency of use was 0.5 times. Regarding intraoperative complications, we observed one bladder injury, but no bowel injuries or major vessel injuries. Postoperative complications occurred in 32 patients (10.1%). One patient with a retained lipoma required reoperation. There was no incidence of chronic pain or mesh infection. The operative time for experienced surgeons (≥20 repairs) was significantly shorter than that of inexperienced surgeons (<20 repairs; P?Conclusions The nTAPP was a safe and useful technique for inguinal hernia repair. Large prospective, randomized controlled trials will be required to establish the benefit of nTAPP.     

Natural history of human prostate gland: Morphometric and histopathological analysis of Japanese men

BACKGROUND: To clarify the pathology of the development of prostatic disorders such as inflammation, cancer, and hyperplasia, we compared histopathological findings of the prostate according to age group. METHODS: Whole-mount sections of prostates were used to assess the relationship between age and prostate weight (n=962), prostate histological composition in the transition zone (TZ) and in the peripheral zone (PZ) (n=68), prostate histopathological findings by zone (n=102), and comparison of latent tumor development by age group (n=1,815). RESULTS: A rapid increase in prostate weight from birth to the 20s was followed by a slow rise thereafter. Volume increases (P<0.01) were observed in all components of glandular epithelium, glandular lumen, and stroma in the TZ from the 40s to 70s inclusive. In the PZ, the epithelial and stromal volumes tended to decrease in an age-dependent manner (P<0.05). Calculi and lymphocyte infiltration were detected at a relatively early age, with a tendency towards an age-dependent increase. Glandular dilation and nodular hyperplasia were noted first in the 30s group, also with a tendency towards age-dependent increase. Latent tumors were first detected in the 30s group (5.6%), and slowly increased thereafter. CONCLUSIONS: There was an age-dependent trend towards prostate glandular dilation and prostate enlargement with inflammation. It was demonstrated that tumor and hyperplasia have a long natural history, usually starting in the fourth decade of life, accompanied by dynamic changes with age in glandular tissue composition as well as cell proliferation activity.     

Mutations in LPAR6/P2RY5 and LIPH are associated with woolly hair and/or hypotrichosis

Background Woolly hair (WH) belongs to a family of disorders characterized by hair shaft anomalies that clinically presents with tightly curled hair, which can be divided into syndromic and non‐syndromic forms of WH. We have recently identified mutations in both LPAR6/P2RY5 and LIPH that are associated with autosomal recessive woolly hair (ARWH). Objective To study the underlying genetic causes of autosomal woolly hair in Pakistani population. Methods We studied 10 Pakistani families with ARWH for mutations in LPAR6/P2RY5 and LIPH and then performed haplotype analysis to confirm their segregation in the families. Results We identified five mutations in LPAR6/P2RY5, among which three were recurrent and two were novel in eight Pakistani families. We then showed that two of the mutations in LPAR6/P2RY5 are founder mutations in Pakistani families. Moreover, we identified two recurrent mutations in the LIPH gene in two Pakistani families. Conclusion Our study extends the spectrum of mutations in LPAR6/P2RY5 gene and underscores those mutations in LPAR6/P2RY5 and LIPH result in similar phenotypes.     

Bumetanide-induced enlargement of the intercellular space in the stria vascularis critically depends on Na+ transport

The intercellular space in the stria vascularis (intrastrial space) is a closed space and isolated from both the endolymph and the perilymph in normal tissue. Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space in association with a decline in the endocochlear potential. It is known that bumetanide inhibits the Na+-K+-2Cl- cotransporter, which is expressed abundantly in the basolateral membrane of marginal cells. We studied ionic mechanisms underlying the bumetanide-induced enlargement of the intrastrial space using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with artificial perilymph containing 100 microM bumetanide caused marked enlargement of the intrastrial space, as reported previously. Removal of K+ from the perilymph did not affect the bumetanide-induced enlargement, whereas removal of Na+ from the perilymph inhibited it almost completely. Perilymph containing 1 mM amiloride also inhibited the enlargement of the intrastrial space almost completely. These results indicate that perilymphatic Na+, but not K+, and amiloride-sensitive pathways are essential to the bumetanide-induced enlargement of the intrastrial space. Two possible pathways could yield these results. Na+ in the perilymph could enter the endolymph via Reissner's membrane or the basilar membrane; Na+ in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na+-K+-ATPase in the basolateral membrane of them. Another, less likely possibility is that Na+ in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na+-K+-ATPase of intermediate cells.     

Netherton syndrome in two Japanese siblings with a novel mutation in the SPINK5 gene: immunohistochemical studies of LEKTI and other epidermal molecules

BACKGROUND: Netherton syndrome (NS) is a severe autosomal recessive disorder characterized by ichthyosiform erythroderma, bamboo hair and atopy. The disease is caused by mutations in the SPINK5 gene, which encodes a putative serine protease inhibitor, LEKTI (lymphoepithelial Kazal-type-related inhibitor). Previous studies have clearly shown a crucial role for LEKTI in skin barrier formation. OBJECTIVES: To identify pathogenic mutations in two Japanese siblings with NS, and further to investigate the consequences of the mutations at the protein level. METHODS: To screen for mutations in the SPINK5 gene, all of its exons and splice junctions were amplified by polymerase chain reaction and directly sequenced. In addition, immunohistochemical staining of LEKTI, desmoglein (Dsg) 1 and elafin was performed with their specific antibodies. RESULTS: Mutation analysis resulted in the identification of compound heterozygous mutations, Q713X and R790X, in the SPINK5 gene of both patients. The former one is a novel mutation. Immunohistochemical studies in one patient demonstrated a complete absence of LEKTI and a strong expression of elafin in the patient's skin. Dsg1 was normally expressed in our patient. CONCLUSIONS: In this report, we describe compound heterozygous mutations in the SPINK5 gene in two Japanese siblings with NS. The result of immunohistochemistry shows LEKTI deficiency and upregulation of elafin in the skin of one patient. Furthermore, our data indicate that degradation of Dsg1 does not always occur in NS.