Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Use of a sensitive enzyme immunoassay for human thyrotropin in the diagnosis of hyperthyroidism

A sensitive, simultaneous sandwich enzyme immunoassay for TSH was evaluated especially for its ability to distinguish hyperthyroid patients from the euthyroid population. A total of 140 patient samples was analzyed by this assay as well as with a two-step sandwich radioimmunoassay. The diagnostic sensitivity of the thyrotropin assay was 92.5% and the specificity was 88%. False negatives by thyrotropin assay included two patients with Graves' disease who were being treated with propranolol at the time of testing and one patient who was considered hyperthyroid while receiving synthroid. Twelve patients with elevated free thyroxine index levels were considered euthyroid and 50% of these had thyrotropin values that were undetectable; most were elderly patients with nonthyroidal illnesses. Although the thyrotropin enzyme immunoassay had good sensitivity and precision for the detection of hyperthyroidism, our data suggest the limitation of a single thyrotropin determination in establishing the euthyroid state, especially in elderly patients with associated nonthyroidal illnesses and hyperthyroxinemia.     

Trigeminal Neuralgia in Pregnancy: A Management Challenge

Pregnancy is known to aggravate pre‐existing chronic painful conditions. Trigeminal neuralgia (TN), albeit a disease of the elderly, may afflict pregnant females, which can further complicate its management. Teratogenic effects of the commonly used drugs on the developing fetus limit pharmacological treatment. Moreover, safety of commonly performed interventional therapies is marred by their inherent fetomaternal effects and more importantly the risk for radiation effects on the fetus due to the use of fluoroscopy. This rare coexistence of TN in pregnancy has not been reported before. Here we present a case of TN in a young woman, whose pain was aggravated when she became pregnant, and she was treated successfully by conventional radiofrequency ablation of the Gasserian ganglion.     

Newer concepts of cancer of the colon and rectum: Clinical evaluation of a radioimmunoassay for CEA

Conclusions Using basically the same reagents and methodology, we have tried to duplicate the optimistic results of Goldet al. Of 578 samples submitted, 393 met the criteria for the study; results for these 393 are presented. Our results indicate that CEA can be detected not only in a smaller proportion of gastrointestinal malignancies than that found by Gold and associates, but also in a similar proportion of inflammatory bowel diseases. Furthermore, we found a significant number of positive in nongastrointestinal malignancies, as well as chronic inflammatory diseases and collagenoses. Therefore, we feel that the assay, in its present form, has limited value as a diagnostic tool in the detection of gastrointestinal malignancies. Better purification procedures, less sensitive methods of detection, or an entirely new approach may produce results of more clinical value than those we have obtained. Symposium presented at the meeting of the American Proctologic Society Las Vegas, Nevada, May 10 to 13, 1971. Presented in part at The Southern Medical Association Meeting, Dallas, Texas, November 16, 1970. Supported in part by grants from the American Cancer Society, Ohio Division, The Randall Foundation, and a donation from Mr. F. Ball.     

Putative roles of a proline–glutamic acid-rich protein (PE3) in intracellular survival and as a candidate for subunit vaccine against Mycobacterium tuberculosis

The proline–glutamic acid (PE) protein family of Mycobacterium tuberculosis (Mtb) plays diverse roles in the pathogenesis and modulation of host immune responses. The uniqueness of conserved regions of PE proteins may be useful to test and validate their corresponding functions. Hence, the present study has been undertaken to demonstrate the role of PE3 (Rv0159c) for persistence, host immune response and immunoprophylaxis. We have expressed Mtb-specific PE3 gene in M. smegmatis (MS) and used the strain to infect J774A.1 macrophage cells and BALB/c mice. It was observed that during the infection, the MS expressing PE3 showed higher bacterial load when compared to infection with wild-type MS. In hypoxic condition, the expression level of PE3 gene was induced in Mtb, which further showed its relevance in the cell survival during hypoxia-induced persistence. The expression level of PE3 in Mtb was markedly induced during chronic stage of murine infection, which reiterated its importance in mycobacterial persistence in the host. The immunization of mice with recombinant PE3 protein stimulated the secretion of TNF, IL-6 and IL-2 cytokines and generated strong protective immunity against challenge with live mycobacteria, which was evidenced by decreased viable bacilli in the lungs, histopathological changes and increased survival of PE3 immunized mice. Conclusively, the results indicated that PE3 plays significant roles in mycobacterial persistence during infection, modulate host immune response and hence could be a prospective candidate for the development of subunit vaccine against tuberculosis.     

Carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with and without coronary artery disease

BACKGROUND: Carotid intima-media thickness and pulse wave velocity are non-invasive markers of atherosclerosis and have been shown to reliably predict presence and extent of atherosclerotic vascular disease. However, studies examining their association with each other have shown inconsistent results. Hence it was sought to assess correlation between carotid intima-media thickness and pulse wave velocity in patients with and without coronary artery disease. METHODS AND RESULTS: Sixty-four patients with angiographically proven coronary artery disease and 84 age-matched individuals without coronary artery disease but having one or more conventional cardiovascular risk factors were included in the study. Individuals with established cerebrovascular disease and peripheral vascular disease were excluded from the study. Carotid intima-media thickness of far wall was measured at three predefined sites (distal common carotid, carotid bifurcation and proximal internal carotid artery) on each side. Brachial-ankle pulse wave velocity was measured non-invasively using VP 1000 (Colin Corporation) automated ABI/ PWV analyzer. There was no significant difference in gender and presence of cardiovascular risk factors in the two groups. Mean and maximum carotid intima-media thickness and brachial-ankle pulse wave velocity were all significantly higher in coronary artery disease patients as compared to patients without coronary artery disease (0.842 v. ( 0.657 mm, p <0.0001; 1.076 v. 0.795 mm, p <0.0001; 1708.63 v. 1547.26 cm/s, p <0.0004 respectively). There was a significant correlation between brachial-ankle pulse wave velocity and both mean and maximum carotid intima-media thickness in patients with coronary artery disease (r = 0.47, p <0.0001 and r=0.41, p < 0.0008 respectively) but not in individuals without coronary artery disease (r=0.01 and -0.1 respectively). CONCLUSIONS: Presence of significant correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with coronary artery disease but absence of the same in individuals without major atherosclerotic vascular disease suggests that the correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity becomes stronger with increasing extent of atherosclerosis.     

A total system approach to sustainable pest management

A fundamental shift to a total system approach for crop protection is urgently needed to resolve escalating economic and environmental consequences of combating agricultural pests. Pest management strategies have long been dominated by quests for “silver bullet” products to control pest outbreaks. However, managing undesired variables in ecosystems is similar to that for other systems, including the human body and social orders. Experience in these fields substantiates the fact that therapeutic interventions into any system are effective only for short term relief because these externalities are soon “neutralized” by countermoves within the system. Long term resolutions can be achieved only by restructuring and managing these systems in ways that maximize the array of “built-in” preventive strengths, with therapeutic tactics serving strictly as backups to these natural regulators. To date, we have failed to incorporate this basic principle into the mainstream of pest management science and continue to regress into a foot race with nature. In this report, we establish why a total system approach is essential as the guiding premise of pest management and provide arguments as to how earlier attempts for change and current mainstream initiatives generally fail to follow this principle. We then draw on emerging knowledge about multitrophic level interactions and other specific findings about management of ecosystems to propose a pivotal redirection of pest management strategies that would honor this principle and, thus, be sustainable. Finally, we discuss the potential immense benefits of such a central shift in pest management philosophy.     

Ciliated Hepatic Foregut Cyst: An Increasingly Diagnosed Condition

Ciliated hepatic foregut cyst is a rare foregut cystic developmental malformation. It presents as a solitary cystic lesion in segment four of the liver. Histologically, it consists of four distinct layers; namely, the inner ciliate columnar epithelium, subepithelial connective tissue, smooth muscle layer, and an outer fibrous layer. Usually asymptomatic and detected incidentally, other modes of presentation can include portal hypertension, obstructive jaundice, and development of malignancy. We present a case of a young asymptomatic woman with a complex cyst in segment four of the liver, who underwent a laparoscopic resection, focusing our discussion on the review of the literature and the diagnostic dilemma encountered in these rare cases.