Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene

Plasma amyloid beta protein (Abeta42) levels and late onset Alzheimer's disease (LOAD) have been linked to the same region on chromosome 10q. The PLAU gene within this region encodes urokinase-type plasminogen activator, which converts plasminogen to plasmin. Abeta aggregates induce PLAU expression thereby increasing plasmin, which degrades both aggregated and non-aggregated forms of Abeta. We evaluated single nucleotide polymorphisms (SNPs) in PLAU for association with Abeta42 and LOAD. PLAU SNP compound genotypes composed of haplotype pairs showed significant association with AD in three independent case-control series. PLAU SNP haplotypes associated significantly with plasma Abeta42 in 10 extended LOAD families. One of the SNPs analyzed was a missense C/T polymorphism in exon 6 of PLAU (PLAU_1=rs2227564), which causes a proline to leucine change (P141L). We analyzed PLAU_1 for association with AD in six case-control series and 24 extended LOAD families. The CT and TT PLAU_1 genotypes showed association (P=0.05) with an overall estimated odds ratio of 1.2 (1.0-1.5). The CT and TT genotypes of PLAU_1 were also associated with significant age-dependent elevation of plasma Abeta42 in 24 extended LOAD families (P=0.0006). In knockout mice lacking the PLAU gene, plasma--but not brain--Abeta42 as well as Abeta40 was significantly elevated, also in an age-dependent manner. The PLAU_1 associations were independent of the associations we found among plasma Abeta42, LOAD and variants in the IDE or VR22 region. These results provide strong evidence that PLAU or a nearby gene is involved in the development of LOAD. PLAU_1 is a plausible pathogenic mutation that could act by increasing Abeta42, but additional biological experiments are required to show this definitively.     

Gelatinous transformation of bone marrow: a study of 43 cases

Gelatinous marrow transformation (GMT) is an uncommon and poorly recognized condition characterized by deposition of seromucinous gelatinous material in the bone marrow stroma. Forty-three cases of GMT were studied in a period of 4 years. There was male preponderance. Fourteen cases were in pediatric age group (less than 12 years). Majority of patients had a preceding history of anorexia, malnutrition and chronic debility. All the patients had anemia. Bone marrow biopsy revealed focal or diffuse GMT. Bone marrow aspirate showed metachromatic dense mucoid material with a few entrapped hematopoietic cells on Giemsa staining. The gelatinous material stained with alcian blue at pH 2.5.     

Intracytoplasmic and intranuclear Reinke's crystals in a testicular Leydig-cell tumor diagnosed by fine-needle aspiration cytology: a case report with review of the literature

We report on the cytopathologic findings of a Leydig-cell tumor of the testis in a young adult male with no evidence of endocrine dysfunction. The preoperative diagnosis was based on fine-needle aspiration cytology (FNAC) alone, which was subsequently confirmed on histopathology. The present case was of interest on account of the paucity of literature regarding the cytodiagnosis of this lesion. In addition, the finding of intracytoplasmic lipofuscin pigment and several intracytoplasmic as well as intranuclear Reinke's crystals served to clinch the diagnosis on FNA. Therefore, the use of FNAC, especially in the presence of diagnostic Reinke's crystals, may vitiate the need for more invasive biopsy procedures in the preoperative diagnosis of testicular Leydig-cell tumors.     

Effects of Vitamin E on airway responses and biochemical parameters in guinea pigs sensitized to ovalbumin

The effect of dietary supplementation with Vitamin E was studied in sensitized guinea pigs. After measurement of baseline airway reactivity and sensitization with ovalbumin, the animals were randomized into two groups: Group A, on a commercial feed and Group B, on dietary supplementation with oral Vitamin E (0.7 IU/kg). These were challenged with inhaled ovalbumin after 4 weeks. The following outcomes were studied: airway responses to ovalbumin inhalation, airway reactivity, sodium and calcium ion influx in isolated tracheal cells, Na+ K+ ATPase and Ca2+ ATPase activity in tracheal homogenate and plasma malonaldehyde. Sensitization increased airway reactivity in Group A but not in Group B. The tracheal cells of animals in Group B showed significantly lower rates of 45Ca and 22Na influx and lower activities of tracheal Na+ K+ ATPase and Ca2+ ATPase as compared to Group A. Plasma malonaldehyde was similar between two groups. We concluded that Vitamin E suppresses the increase in airway reactivity following sensitization and has membrane stabilizing actions.     

Myoglobinuria and transient acute renal failure in a patient revealing hypothyroidism

Muscle involvement in hypothyroidism commonly manifests as fatigue, myalgias, stiffness and slowed reflexes. We report a case of transient acute renal failure related to rhabdomyolysis and myoglobinuria in a 40 year old man that revealed the diagnosis of hypothyroidism with myopathy. The patient had proximal muscle weakness and tenderness, markedly raised muscle enzymes and deranged renal functions that normalised with thyroid replacement therapy. Hypothyroidism, though rare, should be considered a definite and authentic cause of rhabdomyolysis.     

Pitfalls in the diagnosis of epithelioid sarcoma presenting in an unusual site: a case report

The cytologic appearance of epithelioid sarcoma in fine-needle aspiration biopsy cytology (FNABC) smears has not been extensively described. We report a case of epithelioid sarcoma in a 55-year-old male who presented with nodular swellings in the abdominal wall and scrotum. The scrotal swelling was subsequently demonstrated to arise from the vas deferens. We highlight the cytomorphologic, immunocytochemical, and histopathologic features of this rare lesion in an unusual site, with particular emphasis on the dilemma encountered in the cytodiagnosis of this lesion.     

Agreement between CBNAAT,liquid culture and line probe assay for detection of Mycobacterium tuberculosis and anti-tubercular drug resistance in extrapulmonary samples

PurposeCartridge based nucleic acid amplification test (CBNAAT) has been endorsed by the WHO as the screening test for diagnosing extrapulmonary tuberculosis (EPTB). In the present study we report the agreement between CBNAAT (Xpert MTB/RIF), liquid culture (LC) and line probe assay (LPA) for diagnosis of Mycobacterium tuberculosis and detection of drug resistance among EPTB cases.MethodsThe EP samples were subjected to CBNAAT (Xpert MTB/RIF, Cepheid, USA) and wherever possible, to LC (MGIT 960, Becton Dickinson, USA) followed sequentially by first line and second line-LPA (FL-LPA, SL-LPA, Hain Lifescience, Germany) on the isolates.ResultsTotal 566/4080 (13.9%) EP samples were detected positive for M. tuberculosis on CBNAAT. Aspirates from lymph nodes were most often positive (11/30; 36.6%), followed by pus (240/873; 27.5%) and CSF samples (166/104; 15.8%). The detection of M. tuberculosis was more in adults than children except in tissue biopsy samples. Rifampicin resistance was also higher among adults except CSF in which resistance was more in children. Total 185 of 566 (32.7%) CBNAAT positive and 770 of 3510 (21.9%) CBNAAT negative samples could be cultured of which 110/185 (59.4%) and 33/770 (4.3%) respectively turned positive. FL-LPA and SL-LPA of 143 culture isolates showed that 27 isolates had drug resistance, of which 3 (2.1%) were XDR, 11 (7.7%) were Pre-XDR (FQ) and 13 (9.1%) were MDR. Of these 27 resistant isolates, 12 were negative by CBNAAT and two were mislabeled as Rifampicin sensitive or indeterminate based on the unique RpoB gene mutation patterns on LPA. The positive and negative agreements between LC and CBNAAT for detection of M. tuberculosis were 67.1% and 92.7% respectively and between LPA and CBNAAT for rifampicin resistance detection were 98.9% and 92.9% respectively.ConclusionsFor EPTB, CBNAAT should be accompanied with LC wherever possible irrespective of the CBNAAT result.     

Alcohol use following liver transplantation: a comparison of follow-up methods

Alcoholic cirrhosis is one of the most common indications for liver transplantation. Previous researchers have studied rates of return to drinking following transplantation, however, few have employed prospective measures of alcohol use. The authors prospectively studied the alcohol use of patients transplanted for alcoholic liver disease. The authors improved the accuracy of monitoring alcohol use by using various methods for tracking patient's alcohol consumption, and we report on the time to first alcohol use after transplantation comparing these different methods. The authors found that alcohol use can occur very early after transplantation, even within the first 3 months posttransplant. Thirty-eight percent of the patients consumed any alcohol after transplantation. The clinical interviews by the psychiatrist were the most successful method for identifying posttransplant alcohol use. Posttransplant alcohol use was significantly associated with prior nonalcohol substance use (P < 0.025), family history of alcoholism in a first-degree relative (P < 0.025), and prior alcohol rehabilitation experience (P < 0.05) but not with a prior psychiatric history or less than 6 months of pretransplant sobriety. The authors indicate that prospective monitoring, using a combination of methods, is the most accurate approach to identify alcohol consumption. With this type of accuracy, risk factors can be identified and alcohol use can be compared with alcohol-related morbidity posttransplant.     

Severe lower limb defects in exstrophy of the cloaca

We present here a patient with exstrophy of the cloaca associated with severe lower limb defects. The limb malformations include, on the right, a split foot with distal separation of the tibia and fibula, and on the left, attachment of the lower half of the left leg with a two-toed foot at nearly a right angle to the mid left thigh. A review of the literature indicates that 17-26% of patients with cloacal exstrophy also have lower limb defects. We hypothesize that cloacal exstrophy and associated lower limb defects have a related pathogenesis and that both are related to deficiencies of caudal mesoderm or mesodermal differentiation signals. More cases of exstrophy of the cloaca with limb defects need to be reported to better characterize the limb anomalies and to more precisely determine their frequency.