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Biomedical subjects

N Patel

Publications and source records attributed to N Patel.

At least 361 records · Page 20Linked to original sources

Computational tools for exact conditional logistic regression.

Logistic regression analyses are often challenged by the inability of unconditional likelihood-based approximations to yield consistent, valid estimates and p-values for model parameters. This can be due to sparseness or separability in the data. Conditional logistic regression, though useful in such situations, can also be computationally unfeasible when the sample size or number of explanatory covariates is large. We review recent developments that allow efficient approximate conditional inference, including Monte Carlo sampling and saddlepoint approximations. We demonstrate through real examples that these methods enable the analysis of significantly larger and more complex data sets. We find in this investigation that for these moderately large data sets Monte Carlo seems a better alternative, as it provides unbiased estimates of the exact results and can be executed in less CPU time than can the single saddlepoint approximation. Moreover, the double saddlepoint approximation, while computationally the easiest to obtain, offers little practical advantage. It produces unreliable results and cannot be computed when a maximum likelihood solution does not exist.

Adolescent↗

Disease associated balanced chromosome rearrangements (DBCR): report of two new cases.

Disease associated balanced chromosome rearrangements (DBCR) causing truncation, deletion, inactivation or over-expression of specific genes are instrumental in identifying and cloning several disease genes and are estimated to be much more common than anticipated. In one survey, the minimal frequency of combined balanced de novo reciprocal translocations and inversions causing abnormal phenotype is estimated to be 0.17%, a sixfold increase compared to the general population suggesting a causative linkage between the abnormality and the observed phenotypic traits. Here, we report two new cases of apparently balanced de novo translocations resulting in developmental delay and dysmorphic features.

Abnormalities, Multiple↗

An assessment of behavioral aging in the Mongolian gerbil.

Male Mongolian gerbils (Meriones unguiculatus) 14-54 months old (n = 77) were evaluated in a battery of psychomotor (open field, locomotor, and runwheel activity, rotorod performance) and learning (one-way active avoidance in a straight runway and in 14-unit T-maze performance) tests. Body weight and seizure activity were also monitored. According to linear regression analysis, runwheel activity decreased with age; and the number of errors in the 14-unit T-maze increased as a function of age (ps < 0.05). None of the other behavioral measures or body weight were significantly correlated with age. This gerbil strain (Tumblebrook Farms; West Brookfield, MA) tended to be very prone to seizures with 64% of the gerbils experiencing at least one seizure while being tested. Seizures tended to occur when the gerbil was exposed to a novel situation (e.g., initial weighing, placement on the rotorod). An age-related decline in some aspects of psychomotor and learning performance was observed, suggesting the gerbil as an additional mammalian model of aging. The high incidence of seizure activity presented a complicating and confounding variable to the interpretation of the results of the behavioral tests used in the present study. Interventions to control seizure activity (e.g., systematic, controlled breeding; adaptation to apparati) in this model will likely increase its viability as a mammalian model of aging.

Aging↗

The effect of shoulder magnetic resonance imaging on clinical decision making.

One hundred cases were prospectively evaluated to determine the impact of magnetic resonance imaging on clinical decision making in an orthopaedic practice devoted to the treatment of disorders about the shoulder. Each was analyzed for changes in the clinical diagnosis or treatment. A change that either changed the primary diagnosis or type of treatment (operative versus nonoperative) was classified as category one. If additional clinically relevant findings were noted on the imaging studies without altering the primary diagnosis, or if the form of treatment was modified but not changed from operative or nonoperative, it was considered category two. Among the 100 imaging studies reviewed, category one and two changes were observed in 11 and 7 cases, respectively. Magnetic resonance imaging was particularly helpful in diagnosing ganglion cysts about the shoulder, a category one change in three out of three cases. For specific diagnoses a category one or two change was observed in 17% (10 of 59), 29% (4 of 14), 8% (1 of 13),and 100% (2 of 2) for rotator cuff disease, glenohumeral instability, adhesive capsulitis, and biceps disease, respectively. In 35 cases magnetic resonance imaging was considered to be unnecessary for the diagnosis or treatment of the patient. For the 65 patients who underwent magnetic resonance imaging, category one and two changes were noted in 10 and 5 patients, respectively. Statistical significance was demonstrated for category one changes in the entire group (100 cases) and the in subgroup recommended for magnetic resonance imaging (65 cases) (p < 0.05), indicating that the judicious use of magnetic resonance imaging can have a significant increase its impact on clinical decision making. Magnetic resonance imaging was found to be of limited diagnostic value in patients with an isolated primary clinical diagnosis of adhesive capsulitis, glenohumeral or acromioclavicular arthritis, brachial plexopathy, and cervical degenerative disk disease.

Adult↗

Transformation of dopamine and alpha-methyldopamine by NG108-15 cells: formation of thiol adducts.

The catecholamines, alpha-methyldopamine (alpha-MeDA) and dopamine (DA), have been implicated in 3,4-(methylenedioxy)amphetamine (MDA) toxicity. The toxicity and metabolic fate of alpha-MeDA, a metabolite of MDA, and DA, a neurotransmitter released by MDA administration, were examined in NG108-15 cells. Both catechols were found to accumulate intracellularly into NG108-15 cells. alpha-MeDA was about 4 times more toxic than DA in the cells. The depletion of glutathione (GSH) by buthionine sulfoximine (BSO) resulted in a drastic increase (10 times) in the alpha-MeDA mediated toxicity while the toxicity of DA was enhanced by 2 times. DA was largely metabolized to dihydroxyphenylacetic acid (DOPAC) and, to a smaller extent, formed an adduct with GSH. alpha-MeDA was primarily metabolized to a GSH adduct. alpha-MeDA was also metabolized to a product which was identified as the cysteinyl adduct. These adducts were identified by HPLC coelution with authentic standards. The GSH and cysteinyl adducts are presumably formed through conjugation of the thiols with intermediary quinone oxidation products of DA and alpha-MeDA. Previous studies indicate that alpha-MeDA is significantly more toxic than DA, especially under conditions of GSH depletion. The results of this study suggest that alpha-MeDA toxicity may occur through cytoplasmic accumulation and oxidation to a reactive quinone species followed by reaction with vital thiol functions or generation of reactive oxygen species. Cytoplasmic DA levels, on the other hand, appear to be significantly lower due to MAO metabolism and vesicular storage, and therefore, DA appears less likely to form conjugates with thiol groups or participate in possible redox cycling.

3,4-Methylenedioxyamphetamine↗

A rhodopsin is the functional photoreceptor for phototaxis in the unicellular eukaryote Chlamydomonas.

Rhodopsin is a visual pigment ubiquitous in multicellular animals. If visual pigments have a common ancient origin, as is believed, then some unicellular organisms might also use a rhodopsin photoreceptor. We show here that the unicellular alga Chlamydomonas does indeed use a rhodopsin photoreceptor. We incorporated analogues of its retinal chromophore into a blind mutant; normal photobehaviour was restored and the colour of maximum sensitivity was shifted in a manner consistent with the nature of the retinal analogue added. The data suggest that 11-cis-retinal is the natural chromophore and that the protein environment of this retinal is similar to that found in bovine rhodopsin, suggesting homology with the rhodopsins of higher organisms. This is the first demonstration of a rhodopsin photoreceptor in an alga or eukaryotic protist and also the first report of behavioural spectral shifts caused by exogenous synthetic retinals in a eukaryote. A survey of the morphology and action spectra of other protists suggests that rhodopsins may be common photoreceptors of chlorophycean, prasinophycean and dinophycean algae. Thus, Chlamydomonas represents a useful new model for studying photoreceptor cells.

Cell Movement↗

A sheep model for thoracic aortic surgery in the presence of systemic coagulopathy.

Surgical repair of aneurysms, traumatic injuries, or congenital anomalies of the thoracic aorta are associated with high morbidity and mortality mainly as a result of excessive and uncontrollable hemorrhage from diffuse coagulopathy. We developed a model in sheep that simulates this coagulopathic state for experimentation with thoracic aorta surgery. This experimental animal model involves administering a 600-mg aspirin suppository once a day for the 2 days preceding surgery and a final dose on-call to surgery. Prior to cross-clamping the aorta, an intravenous (i.v.) bolus of heparin (400 IU/kg) was administered. Thirty minutes later, the i.v. heparin bolus was repeated. Pre- and intraoperative activated clotting time was 101 +/- 10 s and >1500 s (p < .0001); prothrombin time, 21 +/- 1 s and >100 s (p < .0001); and activated partial thromboplastin time, 20 +/- 1 s and >50 s (p < .0001), respectively. We utilized a partial cross-clamp-and-sew technique to anastomose a woven, gelatin-impregnated, 16-mm tube graft end-to-side to the descending thoracic aorta. Mean total blood loss was 1367 +/- 282 mL, which included mean blood loss from time of release of aortic cross-clamp to close (422 +/- 135 mL) and mean total blood output from chest tube drain (945 +/- 203 mL). The mean time to achieve hemostasis at suture lines after aortic cross-clamp release was 15.5 +/- 6.6 min. In conclusion, a sheep model with induced coagulation defects was successfully developed and reproducible for experimentation involving thoracic aortic surgery.

Anastomosis, Surgical↗

Electrical stimulation of transforming growth factor-beta 1 secretion by human dermal fibroblasts and the U937 human monocytic cell line.

The in vitro effects on human dermal fibroblasts and the U937 human monocytic cell line of three phases of electrical microcurrents generated by the ACE Stimulator were investigated. The growth and viability of growing and confluent dermal fibroblasts were not directly influenced by the separate microcurrent phases. One form of microcurrent (designated phase 1) stimulated both dermal fibroblasts and U937 cells to secrete transforming growth factor-beta 1 (TGF-beta 1), which is an important regulator of cell-mediated inflammation and tissue regeneration, but none of the three phases stimulated secretion of the pro-inflammatory cytokine interleukin-6 by U937 cells. The stimulation of TGF-beta 1 secretion in these experiments was not dramatic (a median increase over control levels of 20-30%), although it could be biologically significant.

Animal Testing Alternatives↗

Malignant nonfunctioning pheochromocytoma occurring in a mixed multiple endocrine neoplasia syndrome.

OBJECTIVE: To present the first documented case of malignant nonfunctioning pheochromocytoma occurring in a mixed multiple endocrine neoplasia (MEN) syndrome. METHODS: We describe the personal and family history of a 34-year-old man with headaches, increased serum prolactin levels, and hyperparathyroidism and review the details of his clinical course and treatment. RESULTS: After diagnosis of a prolactinoma, bromocriptine therapy was implemented but eventually discontinued by the patient when severe headaches recurred. A transsphenoidal resection of a prolactinoma was performed; the patient continued to have abnormally high serum prolactin levels. Subsequent left lower flank pain prompted an exploratory laparotomy, and a left nephroad-renalectomy was performed. Pathologic examination disclosed a 1-cm tumor, consistent with malignant pheochromocytoma. Electron microscopy demonstrated neurosecretory granules. A hypercoagulable state complicated the course postoperatively. Despite chemotherapy, extensive metastatic disease ensued, and the patient died. CONCLUSION: Although pheochromocytomas are usually associated with MEN type IIA and type IIB, this patient had a malignant pheochromocytoma, without the usual clinical and biochemical manifestations, in the setting of MEN type I.

Journal Article↗

A comparison of the incidence of nausea after laparoscopic cholecystectomy and diagnostic laparoscopy.

Thirty-four patients undergoing gynecologic diagnostic laparoscopy and 30 patients undergoing laparoscopic cholecystectomies were followed prospectively for nausea and vomiting 24 hours postoperatively. Diagnostic laparoscopy patients had a significantly higher incidence of nausea and vomiting than laparoscopic cholecystectomy patients with similar anesthetic techniques, duration of surgery, and population parameters. All patients had their stomach contents suctioned after induction. While both procedures involve bowel manipulation, patient position and organ manipulation differ: diagnostic laparoscopy involves the Trendelenburg position and laparoscopic cholecystectomy involves the reverse Trendelenburg; diagnostic laparoscopy involves the uterus, ovaries, and fallopian tubes while laparoscopic cholecystectomy involves mainly the gall-bladder and its appendages. These factors may contribute to the differences found in this study.

Adult↗

Outbreak of kala-azar in Bombay.

A chance diagnosis of kala-azar in a patient referred from Acworth Leprosy Home in Bombay was followed up, resulting in an investigation of a total of 25 patients (inpatients and residents) for the presence of the disease. 30.3% of the patients investigated were found to be suffering from the disease. This confirms the earlier suspicion that Bombay and especially the Acworth Leprosy Home is an endemic area for kala-azar.

Adolescent↗

Dinosaur's feather and chicken's tooth? Tissue engineering of the integument.

The integument forms the interface between animals and the environment. During evolution, diverse integument and integument appendages have evolved to adapt animals to different niches. The formation of these different integument forms is based on the acquisition of novel developmental mechanisms. This is the way Nature does her tissue/organ engineering and experiments. To do tissue engineering of the integument in the new century for medical applications, we need to learn more principles from developmental and evolutionary studies. A novel diagram showing the evolution and development of integument complexity is presented, and the molecular pathways involved discussed. We then discuss two examples in which the gain and loss of appendages are modulated: transformation of avian scale epidermis into feathers with mutated beta catenin, and induction of chicken tooth like appendages with FGF, BMP and feather mesenchyme.

Animals↗

Imaging and clinical characteristics of temporal bone meningioma.

BACKGROUND AND PURPOSE: Imaging characteristics of temporal bone meningioma have not been previously reported in the literature. CT and MR imaging findings in 13 cases of temporal bone meningioma are reviewed to define specific imaging features. METHODS: A retrospective review of our institutional case archive revealed 13 cases of histologically confirmed temporal bone meningioma. CT and MR imaging studies were reviewed to characterize mass location, vector of spread, bone changes, enhancement characteristics, and intracranial patterns of involvement. Clinical presenting signs and symptoms were correlated with imaging findings. RESULTS: Thirteen temporal bone meningiomas were reviewed in 8 women and 5 men, aged 18-65 years. Meningiomas were stratified into 3 groups on the basis of location and tumor vector of spread. There were 6 tegmen tympani, 5 jugular foramen (JF), and 2 internal auditory canal (IAC) meningiomas. Tegmen tympani and JF meningiomas were characterized by spread to the middle ear cavity. IAC meningiomas, by contrast, spread to the cochlea and vestibule. Hearing loss was the most common clinical presenting feature in all cases of temporal bone meningioma (10/13). The presence of tumor adjacent to the ossicles strongly correlated with conductive hearing loss (7/9). CONCLUSION: Meningioma involving the temporal bone is rare. Three subgroups of meningioma exist in this location: tegmen tympani, JF, and IAC meningioma. Tegmen tympani and JF meningiomas spread to the middle ear cavity. IAC meningiomas spread to intralabyrinthine structures. Conductive hearing loss is commonly seen in these patients and can be surgically correctable.

Adolescent↗

Altered lipid profile in liver amoebiasis and its emendation with metronidazole treatment.

Liver amoebic abscess was produced by introducing 16,000 trophozoites of Entamoeba histolytica directly into the livers of growing hamsters. A group of the infected animals received orally 64 mg metronidazole/kg body weight for 5 days from the day of the infection. The treated group was autopsied 7 or 14 days after the treatment. Histologically, liquefaction of large parenchymal areas and biochemically, elevation in cholesterol, triglycerides, bile acids and decrease in phospholipids were observed in infected livers. The infected hamsters exhibited hyperlipidemia and hypocholesterolemia. With metronidazole treatment all the values tended to shift towards control levels. The magnitude of the shift was determined by the post-treatment period.

Animals↗

Hypertensive crisis after a successful placement of an epidural anesthetic in a hypertensive parturient. Case report.

BACKGROUND AND OBJECTIVES: The use of epinephrine-containing local anesthetic solutions in pre-eclampsia is controversial. While epinephrine in local anesthetic solutions has been used without complications in this setting, a hypertensive reaction remains a concern among many clinicians. METHODS: An epidural anesthetic containing epinephrine was administered to a hypertensive parturient for cesarean delivery. When a hypertensive crisis developed, the radial artery was cannulated and administration of sodium nitroprusside was initiated. Arterial blood samples were evaluated for plasma norepinephrine and serum lidocaine concentrations. RESULTS: The introduction of lumbar epidural anesthesia for cesarean delivery using 30 mL 2% lidocaine with 1:200,000 epinephrine resulted in a profound hypertensive reaction, in the patient with pre-eclampsia, despite an adequate level of epidural anesthesia. CONCLUSIONS: Epinephrine-containing local anesthetic solutions may place a hypertensive parturient at significant risk of an acute hypertensive reaction.

Adult↗

Glutathione-dependent biosynthesis and bioactivation of S-(1,2-dichlorovinyl)glutathione and S-(1,2-dichlorovinyl)-L-cysteine, the glutathione and cysteine S-conjugates of dichloroacetylene, in rat tissues and subcellular fractions.

Dichloroacetylene is neurotoxic, nephrotoxic, and nephrocarcinogenic. The present experiments were designed to test further the hypothesis that the glutathione conjugate of dichloroacetylene, S-(1,2-dichlorovinyl)glutathione (DCVG), may be involved in dichloroacetylene-induced neurotoxicity. Hence, the biosynthesis of DCVG from dichloroacetylene and glutathione was studied in cytosolic, microsomal, and mitochondrial fractions of liver, lung, brain, and kidney. Enzymatic formation of DCVG was observed in liver microsomes and mitochondria, but only nonenzymatic formation of DCVG was seen in lung, brain, and kidney. The KM and Vmax for DCVG biosynthesis with glutathione as the variable substrate were 0.40 +/- 0.28 mM and 487 +/- 90.3 nmol/mg protein/min, respectively. No region-specific differences in the rates of DCVG biosynthesis in the brain were observed. In whole brain homogenates, DCVG was hydrolyzed to DCVC, which was biotransformed to pyruvate and S-(1,2-dichlorovinyl)-3- mercaptopyruvate, indicating cysteine conjugate beta-lyase-catalyzed beta-elimination and transamination reactions in cerebellar tissues. These findings indicate that the glutathione-dependent bioactivation of dichloroacetylene may be involved in the dichloroacetylene-induced neurotoxicity.

Acetylene↗