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Biomedical subjects

U Joshi

Publications and source records attributed to U Joshi.

At least 19 recordsLinked to original sources
PubMed2005

Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET).

PURPOSE: To determine the concordance of a prototype dual head coincidence camera (LSO-PS) and full ring PET (BGO-PET) using (18)F-fluorodeoxyglucose (FDG) in the evaluation of pulmonary nodules (PNs). MATERIALS AND METHODS: Patients referred for evaluation of < or =3 PNs (< or =3 cm diameter) were prospectively studied on the same day with both BGO-PET and LSO-PS. Imaging was performed at 60 and 120 min after injection of 370MBq FDG, respectively. Images were independently interpreted by four observers with each observer blinded to the other modality for the same patient. Lesions were scored in terms of relative intensity versus background. Non-attenuation corrected (nonAC) BGO-PET was used as the reference test. RESULTS: Forty-seven patients with 54 PNs (mean diameter 1.7 cm, S.D. 0.7) were included. Twelve nodules were in the < or =1.0 cm - 27 in the 1.1-2.0 cm - and 15 in the 2.1-3.0 cm range. Interobserver agreement was similar for both FDG imaging modalities. Using a sensitive assessment strategy with LSO-PS (> or = faint intensity deemed positive), there was a 97% (38/39, 95%CI 87-100%) concordance with BGO-PET and one false positive case with LSO-PS. Conservative reading (moderate or intense intensity deemed positive) resulted in a 92% (36/39, 95%CI 80-97%) concordance with BGO-PET, without false positives. The only lesion missed by LSO-PS using both assessment strategies involved a nodule 1.5 cm diameter that demonstrated moderate increased FDG uptake on BGO-PET. CONCLUSION: Depending on the test positivity criteria, LSO-PS demonstrates a high concordance (92-97%) with nonAC BGO-PET for the characterization of pulmonary nodules.

Aged↗
PubMed2005

Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning.

Proteus syndrome is a rare, sporadic genetic disorder characterized by overgrowth of multiple different tissues in a mosaic pattern. It is associated with connective tissue nevi, epidermal nevi, disproportionate overgrowth of multiple tissues, vascular malformations, characteristic tumors, and specific facial anomalies. Joseph Merrick, popularly known as the Elephant Man, is now believed to have suffered from Proteus syndrome. A case of Proteus syndrome and associated findings on bone scintigraphy are presented.

Child↗
PubMed2004

In search of an unknown primary tumour presenting with extracervical metastases: the diagnostic performance of FDG-PET.

A retrospective study was carried out to determine the performance of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with unknown primary tumours presenting with metastases external to the neck. All patients referred to an academic PET centre (July, 1997 to December, 2000) presenting with an extracervical metastasis and no prior systemic therapy were eligible. The minimum follow-up period was 11 months. From 63 eligible cases, known metastases were FDG avid in all but one neuroendocrine process. PET scans were retrospectively classified as positive for a primary tumour (n=29), i.e. revealing at least one anatomical site suspected to be the primary tumour. This was confirmed in 16, either by histology (n=10) or radiological and clinical follow-up (n=6). There were four false positive cases. In nine patients, the primary tumour was never confirmed. Of the remaining 33 negative PET scans the primary tumour was clinically not found in 18. Follow-up and additional pathology investigations demonstrated the primary tumour in 15. A survey on clinical usefulness of PET (response rate 83%) suggested that PET positively contributed to diagnostic understanding in 29 of 52 evaluable cases. Applied late in the diagnostic trajectory, approximately four patients need to be scanned by PET in order to find one primary tumour. However, in addition to direct demonstration of unknown primaries, there appears to be a positive effect on the diagnostic work-up of these patients of a similar magnitude.

Adult↗
PubMed2003

Prospective use of serial questionnaires to evaluate the therapeutic efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in suspected lung cancer.

BACKGROUND: A study was undertaken to study the effect of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the diagnosis and management of clinically problematic patients with suspected non-small cell lung cancer (NSCLC). METHODS: A prospective before-after study was performed in a cohort of all 164 patients (university/community settings) referred for PET between August 1997 and July 1999. PET was restricted to cases where non-invasive tests had failed to solve clinical problems. The impact on diagnostic understanding and management was assessed using questionnaires (intended treatment without PET, actual treatment choice after PET, post hoc clinical assessment). RESULTS: Diagnostic problems especially pertained to unclear radiological findings (n=112; 63%), mediastinal staging (n=36; 20%), and distant staging issues (n=16; 9%). PET findings were validated by reviewing medical records. PET had a positive influence on diagnostic understanding in 84%. Improved diagnostic understanding solely based on PET was reported in 26%. According to referring physicians, PET resulted in beneficial change of treatment in 50%. Cancelled surgery was the most frequent change in treatment after PET (35%). CONCLUSION: FDG PET applied as "add on" technology in patients with these clinical problems appears to be a clinically useful tool, directly improving treatment choice in 25% of patients. The value of increased confidence induced by PET scanning requires further evaluation.

Carcinoma, Non-Small-Cell Lung↗
PubMed2001

Prophylactic efficacy of amifostine and its analogues against sulphur mustard toxicity.

The successful implication of the chemical weapons convention stimulated research with a new vigour on the destruction of the stockpiled sulphur mustard (SM). A prophylactic agent for SM will be very useful for personnel engaged in the destruction of SM and during inspections by the Organisation for the Prohibition of Chemical Weapons. Due to simple method of preparation, SM can be used clandestinely during war or by terrorist groups. Inspite of research over several decades no satisfactory prophylactic or treatment regimen has evolved for SM. Amifostine an organophosphorothioate, originally developed as a radioprotector, and its analogues were evaluated as a prophylactic agent for SM. Three analogues by varying the chain length and substitution at the sulphur atom were synthesised and coded as DRDE-06, DRDE-07 and DRDE-08. LD(50) of amifostine and its analogues were estimated through intraperitoneal (i.p.) route. For the protection studies, amifostine and its analogues were administered i.p. in mice, 30 min before dermal (percutaneous) application of SM. The dose of the prophylactic agent was 0.2 LD(50) (i.p.) and that of SM was 152 mg/kg (undiluted) equal to 19-fold LD(50) of SM. Amifostine and one of its analogues, DRDE-07 gave significant protection. Further studies were carried out using amifostine and DRDE-07, and both of them significantly protected mice against SM (155 mg/kg, in PEG 300, equal to 19 LD(50)) when they were administered i.p. either 30 min before or simultaneously. LD(50) of amifostine and DRDE-07 were also estimated through the oral route (1049 or 1248 mg/kg, respectively). Prophylactically administered amifostine and DRDE-07 (0.2 LD(50), p.o.) significantly protected the mice against dermally applied SM (155 mg/kg, in PEG 300, equal to 19 LD(50)). The protection offered by DRDE-07 was better than that of amifostine by the oral route. DRDE-07 (0.2 LD(50), p.o.) also protected significantly with respect to the decrease in body weight and the depletion of GSH induced by SM. DNA damage induced by SM was also significantly reduced by amifostine and DRDE-07 (0.2 LD(50), p.o.). Further studies are in progress on the various pharmacological and toxicological properties of DRDE-07.

Administration, Oral↗
PubMed1998

An orthotopic model of human pancreatic cancer in severe combined immunodeficient mice: potential application for preclinical studies.

Pancreatic adenocarcinoma is one of the most incurable and least understood of all human cancers. It is the fourth leading cause of cancer-related mortality in males (after lung, prostate, and colon) and in females (after lung, breast, and colon) in the United States with <2-3% of patients surviving >5 years. In an attempt to search for more effective therapies for this disease, we report here, for the first time, an effective treatment, the combination of gemcitabine and auristatin-phenethylamine (PE), against an orthotopic implantation of a human pancreatic adenocarcinoma cell line (HPAC) in severe combined immunodeficient (SCID) mice. Tumor implantation was performed by injecting 100 microl of the HPAC cell suspension (1 x 10(6) cells) directly into the pancreas of 5-week-old SCID mice. After implantation, tumor formation was checked twice a week. All palpable tumors were detected within 21 days (100% take rate), and tumors were confirmed histologically to be pancreatic adenocarcinoma. For the subsequent efficacy trial, tumor-bearing SCID mice were randomized into four groups with five mice in each group. One served as a control, the second received gemcitabine alone (2.5 mg/kg/injection i.p.), the third received auristatin-PE alone (2.0 mg/kg/injection i.v.), and the fourth group received the combination of gemcitabine (i.p.) and auristatin-PE (1.5 mg/kg/injection i.v.). All animals were euthanized 7 days after the completion of their treatments, and the pancreases were resected. Histological examination revealed the tumors to be adenocarcinoma. The tumors were composed of diffuse sheets of cells interrupted by glandular spaces containing secretory material. Cytologically, the tumor cells were large, pleomorphic, and hyperchromatic. Many cells contained intracellular lumina containing mucin. Immunohistochemical studies showed strong p21WAF1 (p21) expression but no immunoreactivity with p53 and Her-2/neu antibodies. The mean pancreatic weight in the gemcitabine/auristatin-PE combination group was significantly (P = 0.014) lower (0.84 +/- 0.639 g) when compared with those of the control (2.91 +/- 1.19 g) and gemcitabine alone (1.84 +/- 0.796 g; P = 0.064) groups. In addition, the mean weight in the combination group approached statistical significance when compared with the auristatin-PE group alone (1.16 +/- 0.635 g; P = 0.028). We conclude that the combination of gemcitabine and auristatin-PE is an effective treatment against HPAC tumors in this xenograft model and more effective than treatment with either gemcitabine or auristatin-PE alone and could be considered for future animal studies with pancreas cancer and/or for human clinical trials.

Adenocarcinoma↗
PubMed1986

Irreversible suppression of calcium entry into nerve terminals by methylmercury.

Measurements of uptake of 45Ca into rat forebrain synaptosomes depolarized with high K+ and EPP amplitudes at the rat neuromuscular junction were used to assess the effects of methylmercury (MeHg) on voltage-dependent Ca++ uptake and subsequent transmitter release at model central and peripheral synapses. The objectives were to: determine whether MeHg altered uptake of 45Ca into purified synaptosomes depolarized by high K+; compare its effects with those produced by HgCl2; ascertain whether the "fast" or "slow" components of Ca++ uptake were affected preferentially by MeHg; and determine whether a functional correlate to the effects on 45Ca uptake could be observed electrophysiologically at the mammalian neuromuscular junction. HgCl2 (10-500 microM) produced a concentration-dependent decrease of total depolarization-induced 45Ca uptake. Peak inhibition occurred at 200 microM Hg++ which suppressed nerve terminal Ca++ uptake to approximately 5% of Hg-free control values, a result similar to that obtained previously by others. Similarly, MeHg also suppressed total 45Ca uptake although the maximal inhibition produced (70% at 200 microM MeHg) was less than that produced by HgCl2. The effect of MeHg was apparent both in nonpreviously depolarized synaptosomes after a 1-sec depolarization ("fast uptake") and after 10-sec incubation in synaptosomes predepolarized with 41 mM K+ in Ca-free solutions before addition of MeHg and 45Ca ("slow uptake"). A significant decrease in the slow phase of 45Ca uptake occurred with 200 and 500 microM MeHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1979

Serum gonadotropins and testosterone in infertile patients with varicocele.

Serum concentrations of gonadotropins and testosterone in 25 infertile men with varicocele were compared with those in control men and men with idiopathic oligo-azoospermia. No significant difference was found in values of serum follicle-stimulating hormone (FSH) (14.9 +/- 13.6 mIU/ml), luteinizing hormone (LH) (24.9 +/- 19.1 mIU/ml), and testosterone (5.0 +/- 2.1 ng/ml) when the group with varicocele was compared with either the control group (FSH, 7.0 +/- 3.2 mIU/ml; LH, 23.6 +/- 16.0 mIU/ml; testosterone, 5.3 +/- 1.8 ng/ml) or the group with idiopathic oligo-azoospermia (FSH, 23.0 +/- 22.69 mIU/ml; LH, 36.7 +/- 24.1 mIU/ml; testosterone, 5.31 +/- 2.3 ng/ml). However, compared with the control group, there was a significant elevation of serum FSH levels in patients with varicocele whose testicular biopsy score counts were between 1 and 4. The importance of preoperative determination of the serum FSH level is discussed.

Biopsy↗