The Role of 18 FDG PET-CT in Evaluation of Unknown Primary Tumours.

An unknown primary tumor (UPT) is defined as a biopsy-proven malignancy whose anatomic origin remains unidentified after diagnostic evaluation. The estimated incidence of unknown primary tumors is 2 %-7 % of all malignancies. In 15-25 % of cases, the primary site cannot be identified even on postmortem examination. The management of these patients remains a clinical challenge. The aim of this study was to determine the role of 18FDG-PET CT in evaluation of primary tumor and its influence on therapeutic management. Fifty patients with histologically-proven metastases of UPT were included. For all patients, the conventional diagnostic work-up was unsuccessful in localizing the primary site. Whole-body PET/CT images were obtained approximately 60 min after intravenous injection of 350-425 MBq of (18) F-FDG. PET/(CT) depicted histologically verified primary tumors in 21of 46 patients (P > .05), achieving detection rates of approx. 61 % in patients presenting with cervical lymph node metastases from unknown primary tumors, and 40 % in those with extra cervical disease presentation. A positive predictive value of 72 % to 92 % was seen for all patients, depending on category of clinical presentation. In this study, PET/CT detection of additional metastases in 14.2 % (3 cases out of 21 true positives) influenced change in management plan. Considering recent studies and the results of this study, whole body FDG-PET/CT has to be considered a useful tool in evaluating metastases from an UPT, allowing an identification of primary tumors in 42 %, and modifying the stage of the disease and oncological treatment in about 50 % of cases. These results suggest the use of PET/CT with FDG in an early phase of the diagnostic evaluation to optimize the management of these patients.

Cervical mediastinoscopy: re-evaluation of an old technique in era of new imaging technology.

CONTEXT: With the advent of modern anatomical and functional imaging technologies, application of cervical mediastinoscopy has decreased in diagnosis and staging of mediastinal diseases. AIM: To evaluate the usefulness of cervical mediastinoscopy in assessing the mediastinal disease when imaging modalities are non-diagnostic. SETTINGS AND DESIGN: Retrospective analysis of records of a tertiary care hospital. PATIENTS AND METHODS: Thirty-nine patients with mediastinal pathology of varied aetiologies underwent cervical mediastinoscopy. Pre- and post-operative diagnosis was compared. RESULTS: In 34 out of 39 cases (87.5%), cervical mediastinoscopy provided a confirmatory final diagnosis. One case had a major complication in the form of recurrent laryngeal nerve palsy. CONCLUSION: Cervical mediastinoscopy is useful, minimally invasive modality in a scenario where anatomical and functional imaging tools are non-diagnostic.

Assessment and occurrence of various heavy metals in surface water of Ganga river around Kolkata: a study for toxicity and ecological impact.

A study was conducted during November, 2005-October, 2006 to evaluate the surface water quality of river Ganga around Kolkata. The samples were analyzed for a number of physico-chemical parameters using standard laboratory procedures and giving prime thrust to determine the heavy metal concentrations (Fe, Mn, Cu, Zn, Pb, Cd, Cr, and Ni) of surface water at four different locations of the river Ganga around Kolkata from two points (middle of the river stream and a discharge point) at each location. Out of 96 samples analyzed, Fe, Mn, Cu, Zn, and Ni were detected in 71, 47, 38, 60, and 45 samples in the concentrations ranging from 0.013 to 5.49, 0.022 to 1.78, 0.003 to 0.033, 0.005 to 0.293, and 0.045 to 0.24 mg L(-1), respectively. Cd and Pb were detected in six and 21 samples in the range of 0.005 to 0.006 and 0.05 to 0.53 mg L(-1), respectively. But Cr was not detected in any of the samples analyzed. The metals exhibited no significant variation with respect to sampling locations as well as discharge points. However, the concentration of those metals varied with season, being higher in rainy and lower in winter season.

Tracheal necrosis with surgical emphysema following thyroidectomy.

Tracheal necrosis after thyroidectomy is an extremely rare event with only a few published reports. We present a case of a 65-year-old male who developed rapidly progressive surgical emphysema of face and upper thorax on the seventh day following total thyroidectomy. Prompt surgical exploration of neck revealed a tracheal rent at the level of the second tracheal ring. This hole was then refashioned into a formal tracheostomy. Patient had an eventful recovery. Tracheostomy was closed by the 14th day. The complication was probably related to tracheal injury sustained due to electro-coagulation and subsequent secondary infection.

PINK1 protein in normal human brain and Parkinson's disease.

Parkinson's disease is a common incurable neurodegenerative disease whose molecular aetiology remains unclear. The identification of Mendelian genes causing rare familial forms of Parkinson's disease has revealed novel proteins and pathways that are likely to be relevant in the pathogenesis of sporadic Parkinson's disease. Recently, mutations in a novel gene, PINK1, encoding a 581 amino acid protein with both mitochondrial targeting and serine/threonine kinase domains, were identified as a cause of autosomal recessive parkinsonism. This provided important evidence for the role of the mitochondrial dysfunction and kinase pathways in neurodegeneration. In this study, we report the first characterization of the PINK1 protein in normal human and sporadic Parkinson's brains, in addition to Parkinson's cases with heterozygous PINK1 mutations. The possible role of the PINK1 protein was also assessed in a number of neurodegenerative diseases characterized by proteinaceous inclusions. For these studies, rabbit polyclonal antibodies were raised against two peptide sequences within the N-terminal hydrophilic loops of PINK1 protein. Using immunohistochemistry and western blotting we were able to demonstrate that PINK1 is a ubiquitous protein expressed throughout the human brain and it is found in all cell types showing a punctate cytoplasmic staining pattern consistent with mitochondrial localization. Fractionation studies of human and rat brain confirm that PINK1 is localized to the mitochondrial membranes. In addition, we show that PINK1 is detected in a proportion of Lewy bodies in cases of sporadic Parkinson's disease and Parkinson's disease associated with heterozygous mutations in the PINK1 gene, which are clinically and pathologically indistinguishable from the sporadic cases. PINK1 was absent in cortical Lewy bodies, in neurofibrillary tangles in Alzheimer's disease, progressive supranuclear palsy and corticobasal degeneration, and in the glial and neuronal alpha-synuclein positive inclusions in multiple system atrophy. These studies provide for the first time in vivo morphological and biochemical evidence to support a mitochondrial localization of PINK1 and underpin the significance of mitochondrial dysfunction in the pathogenesis of nigral cell degeneration in Parkinson's disease.

Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes: broadening the clinical picture to include progressive supranuclear palsy.

The frontotemporal lobar degenerations (FTLDs) are a group of disorders in which the clinical picture is not necessarily predictive of the underlying neuropathology. The FTLD with ubiquitin-only-immunoreactive neuronal changes (FTLD-U) subtype is pathologically characterized by ubiquitin-positive, tau and alpha-synuclein-negative neuronal cytoplasmic inclusions in the frontotemporal cortex and hippocampal dentate fascia. When similar pathological changes are accompanied by histological features of motor neuron disease (MND), the term FTLD-MND is used. The latter pathological changes may be found in patients with or without clinical evidence of MND. We retrospectively reviewed the clinical details of three patients with a rapidly progressive, levodopa-unresponsive bradykinetic-rigid syndrome and frontal cognitive impairment. A diagnosis of progressive supranuclear palsy (PSP) had been considered in all three cases at initial presentation. Two of the cases fulfilled clinical diagnostic criteria for PSP, which was the final clinical diagnosis during life. Pathological analysis showed typical histological appearances of FTLD-MND in two cases and of FTLD-U in one case. Semi-quantitative analysis of pathological load seemed to correlate with the clinical phenotype. FTLD-U or FTLD-MND should be considered in the differential diagnosis of progressive frontal dementia with an akinetic rigid syndrome and supranuclear gaze palsy or Steele-Richardson-Olszewski disease.

Potentiality of tricyclic compound thioridazine as an effective antibacterial and antiplasmid agent.

Thioridazine (Th), which is therapeutically used in psychiatric patients, was found to possess conspicuous antimicrobial activity when tested against 316 strains belonging to a number of Gram positive and Gram negative bacteria. Although Staphylococcus aureus, Vibrio chloerae and V. parahaemolyticus were found to be most sensitive, Th was highly bactericidal against S. aureus and bacteriostatic for vibrios and other Gram negative organisms. In the study of antiplasmid/curing effect of Th on twelve multiply antibiotic and Th resistant bacteria, it was observed that elimination of R plasmids was facilitated by choice of optimal concentration of Th. Significant elimination of single and combined antibiotic resistance occurred in E. coli and Shigella flexneri and not in S. aureus.

Posttranslational modifications of cardiac and skeletal muscle proteins by reactive oxygen species after burn injury in the rat.

OBJECTIVE: To determine the involvement of oxidative damage in muscle wasting after burn injury. SUMMARY BACKGROUND DATA: Burn injury damages tissue at the site of the burn and also affects peripheral tissue. There is evidence to suggest that reactive oxygen species may be generated in increased amounts after burn, and these may contribute to wound healing and to posttranslational modifications of tissue constituents distant from the wound site. METHODS: The oxidation of muscle proteins was assessed, using the dinitrophenylhydrazine assay for carbonyl content, in muscles of rats after a full-thickness skin scald burn covering 20% of the total body surface area, over a 6-week period. In this model, rats failed to incur normal body weight or muscle weight gain. RESULTS: Soleus, extensor digitorum longus, diaphragm, and heart ventricle proteins were oxidatively damaged after injury. The extent of tissue protein oxidation, however, differed depending on the time points studied. In general, higher levels of protein carbonyl group formation, an indicator of oxidative damage, were found to occur within 1 to 5 days after injury, and the oxidized protein content of the various tissues decreased during the later stages. Both sarcoplasmic and myofibrillar carbonyl-containing proteins accumulated in diaphragm 3 days after burn injury and were rapidly removed from the tissue during a 2-hour in vitro incubation. This coincided with increased proteolytic activity in diaphragm. CONCLUSIONS: These observations suggest that the loss of proteins modified by reactive oxygen species may contribute to the burn-induced protein wasting in respiratory and other muscles by a proteolytically driven mechanism.

Determination of tungsten in niobium-tantalum, vanadium and molybdenum bearing geological samples using derivative spectrophotometry and ICP-AES.

Two different procedures, one using derivative spectrophotometry and another using inductively coupled plasma atomic emission spectrometry (ICP-AES) have been developed for the determination of tungsten in niobate-tantalates, tin slag samples, ores, concentrates and vanadium and molybdenum bearing geological materials. In the first method involving derivative spectrophotometry, 0.05-0.5 g of the sample is fused with sodium hydroxide, the tungsten is extracted by leaching the melt with distilled water and estimated as thiocyanate using a second derivative spectrophotometric method in the presence of interferents, i.e. Nb, Mo and V, without separating them. Mixtures of tungsten with V, Nb and Mo are used for standardizing the various parameters like zero-crossing wavelength, wavelength range, etc. Tolerance limits for V, Nb and Mo have also been evaluated. In the second method involving ICP-AES, 0.05-0.5 g of sample is fused with KHSO(4) to a clear melt and dissolved in ammonium oxalate solution. Ammonium hydroxide precipitation is then carried out to separate Nb and Ta as hydroxides and the filtrate is boiled with nitric acid to destroy the oxalates before aspiration into the plasma for measurement of tungsten values by ICP-AES using the 207.911 nm emission line. Both methods have been applied to niobate-tantalate and tin slag samples and the results obtained are reported in this paper. The values obtained by both methods are in good agreement with each other. The proposed methods have also been applied to the determination of tungsten in two Canadian Certified Reference Standards (CT-1 and MP-2) and the values obtained are in good agreement with the certified values and the R.S.D.% in case of the ICP-AES method varied from 1-2% at >1000 mug g(-1) level to 9.4% at the 20 mug g(-1) level whereas the R.S.D.% in case of the derivative method varied from 1 to 7.8%.

Sepsis increases oxidatively damaged proteins in skeletal muscle.

BACKGROUND: Muscle wasting and negative nitrogen balance are common findings in septic patients. It is not clear what signals this loss of body protein. Proteins modified by reactive oxygen species have been shown to be rapidly degraded. OBJECTIVE: To test the hypothesis that sepsis results in an increased amount of oxidatively damaged proteins in skeletal muscle. METHODS: Exposure of proteins to reactive oxygen species results in the incorporation of carbonyl groups into amino acids with metal binding sites. The formation of carbonyl group derivatives in sarcoplasmic and myofibrillar proteins was measured in the extensor digitorum longus and soleus muscles of septic rats 4 to 48 hours after cecal ligation and puncture and in control rats that underwent sham operation. RESULTS: Protein carbonyl content was increased 8 and 16 hours after cecal ligation and puncture in the extensor digitorum longus and soleus muscles, respectively. When muscles were incubated in vitro, the carbonyl content in protein decreased in muscles from septic rats but not in muscles from rats that had the sham operation. The loss of carbonyl groups in incubated septic muscles occurred also in energy-depleted muscles. CONCLUSIONS: Muscle proteins are oxidatively damaged during sepsis and an energy-independent proteolytic pathway participates in the degradation of these proteins. Damage to muscle proteins by reactive oxygen species may signal the selective removal of postsynthetically modified proteins, contributing to accelerated muscle protein degradation in sepsis.

Role of computed tomography in preoperative evaluation of esophageal carcinoma.

The utility of computed tomography in pretherapy assessment of esophageal carcinoma is reviewed. Computed tomographic findings in 78 patients with histologically proved esophageal carcinoma were corelated with findings at surgery and histopathology. Computed tomography (CT) was found to be fairly accurate in assessing tumor extent, invasion of adjacent mediastinal structures and distant metastases but was of no help in detecting periesophageal lymph node involvement. The tracheobronchial tree invasion was detected with an overall accuracy of 96% whereas the same for invasion of aorta, percardium and gastroesophageal junction was 86%, 88% and 78% respectively. The sensitivity for the detection of periesophageal and perigastric lymphadenopathy was low (9% and 0% respectively) but was acceptably high in celiac lymphadenopathy (70%). CT is an excellent non invasive modality in pretherapy assessment of esophageal carcinoma and can guide the surgeon in determining the appropriate therapy.

Studies on the existence of synergism between different antibiotics and a phenothiazine tranquilizer, promazine, possessing antimicrobial property.

Different antibiotics were tested for their capacity to exhibit synergism when used in combination with promazine (Pr), a tranquilizer endowed with powerful antimicrobial property. For this purpose the minimum inhibitory concentration (MIC) of different antibiotics and Pr was first determined by spot inoculation technique on nutrient agar plates to select the concentrations of the antibiotics and Pr to be used as well as the sensitive strains. It was observed that Pr in combination with tetracycline (Tc) demonstrated a marked enhancement of the inhibitory capacity of each drug, both against the Gram-positive and Gram-negative bacteria, following disc diffusion technique. The in vitro findings were further substantiated with the in vivo effects of Pr along with Tc using Salmonella typhimurium NCTC 74 as the challenge strain in mice. The synergism obtained was further corroborated in terms of the increase in the size of their inhibition zones compared with their unaltered individual zones to determine the level of significance. This result was also confirmed by the checkerboard test using doubling dilutions of both the agents.

The effect of thyrotropin-releasing hormone stimulation on serum levels of gonadotropins in women during the follicular and luteal phases of the menstrual cycle.

Thyrotropin-releasing hormone (TRH) can stimulate the secretion of adenohypophyseal thyroid-stimulating hormone and prolactin (PRL). The effect of TRH on gonadotropin secretion has not been well defined. This study investigated the effect of TRH administration on the peripheral levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during the early follicular and midluteal phases of the menstrual cycle in five ovulatory, euthyroid, and normoprolactinemic women. Two hundred micrograms of TRH were administered intravenously on days 3 to 5 and on days 21 to 23 of the same cycle. LH and FSH were measured prior to and every 30 minutes for 2 hours following TRH injection. Ovulation was confirmed in all cycles by midluteal progesterone. All women had normal thyroid-stimulating hormone (TSH) and PRL responses to TRH stimulation in both cycle phases. Baseline and stimulated gonadotropin levels were analyzed by analysis of variance. Thirty minutes following TRH infusion, follicular and luteal levels of LH (mIU/ml, mean +/- standard error of the mean) significantly increased from 6.0 +/- 0.8 to 8.0 +/- 1.1 (P less than 0.005), and from 4.8 +/- 0.6 to 7.6 +/- 0.7 (P less than 0.005), respectively. Levels of FSH increased during both phases of the cycle, but the elevation was not statistically significant. These results suggest that TRH can stimulate gonadotrope secretion of LH, but not of FSH, in both the follicular and luteal phases of the cycle.

Extent of utilisation of maternal care services of P.H.C. by the families of a rural area.

PIP: The utilization of the maternal health care services offered by an upgraded primary health care (PHC) facility in a rural area of West Bengal, India was assessed. Information on the use of the maternal services by pregnant women over a 5-year period was collected from a house-to-house sample of 100 families living less than 1 hour away from the health facility and having at least 1 child born into the family in the previous 5-year period. Women in 58% of the families used the prenatal services of the facility, 6% received prenatal care from private practitioners, and 36% received no prenatal care. Reasons given for not using the facility were 1) using the clinic was too time consuming, 2) the staff was unfriendly, 3) a lack of interest in the services provided. There was no significant differences between prenatal service utililizers and nonuser in regard to caste differences. Utilizers were somewhat more likely to live in households with a literate household head than nonusers. The number of visits made by the utilizers ranged from 1-5, but many respondents had difficulty recalling the exact number. Utilizers were no more likely than nonusers to use the delivery services of the PHC. Among the 58 women who used either the prenatal services of the PHC or of private practitioners, 34 had their deliveries at the PHC, 23 at home and 1 in the hospital. Among the 42 women who received no prenatal care, 15 gave birth at the PHC center, 20 at home, and 4 at nursing homes. Home deliveries were conducted either by untrained midwives or by family members. 3 cases of neonatal tetanus and 1 case of maternal tetanus were reported in the community during the 5 year period. All of these births occurred at home. Only 6% of the 100 mothers used the postnatal services of the PHC center. The findings indicate that the provision of upgraded services by itself is insufficient to overcome the lack of health care motivation on the part of the target population.^ieng

Female hormones reduce neutrophil responsiveness in vitro.

Neutrophils were preincubated with 17 beta-estradiol and progesterone to determine the effects of these hormones on chemotactic peptide-stimulated superoxide anion (O2-) generation and degranulation. At pharmacologic levels 17 beta-estradiol was more active than progesterone with respect to inhibition of O2- generation as well as degranulation. An increase of preincubation time from 5 minutes to 25 minutes increased the percent inhibition. When 17 beta-estradiol and progesterone were combined at levels which approximate those measured during gestation, there was small but significant inhibition of O2- generation. Dexamethasone at equal molar concentration inhibited O2- generation only after 25 minutes of preincubation and at no time reached the level of inhibition attained by either of the sex hormones alone. Both estradiol and progesterone at pharmacologic levels significantly inhibited beta-glucuronidase and lysozyme release, whereas dexamethasone did not inhibit degranulation despite prolonged preincubation. Neutrophils isolated from women during various phases of the menstrual cycle and during the third trimester of pregnancy did not differ with respect to chemotactic peptide-stimulated O2- generation. These data suggest that inhibition of neutrophil responses requires the continuous presence of pharmacologic levels of estradiol and progesterone.