Distinguishing between periampullary carcinoids and carcinomas--is this possible preoperatively?

It is difficult to distinguish between carcinoid tumors of the pancreatic head and periampullary region and carcinomas preoperatively. Between 1996 and 2002, 125 consecutive pancreaticoduodenectomies done by us for periampullary tumors (14 carcinoids, 111 carcinomas) were analyzed. Patients with carcinoid tumors had significantly younger mean age (48 vs. 54 years), longer history (32 vs. 8 weeks), lower serum total bilirubin levels (1.4 vs. 6.3 mg/dL) and on CT scan, had larger, well-localized tumors (5 cm vs. 2 cm). Their postoperative course was better with no mortality or major morbidity, whereas after resection for carcinoma 7 (6.3%) patients died and 30 (27%) had major postoperative complications. Thus, a tumor of this region in a young patient with indolent history, low bilirubin level and with CT scan depicting a large expansile lesion suggests a carcinoid. Such tumors may be safely resected with low postoperative morbidity and mortality and good long-term prognosis.     

Fetal antigen retained by mature neurons and ependyma studied with a monoclonal antibody (6B9)

A mouse monoclonal antibody (MAb 6B9, isotype IgM) was raised against autopsy tissue samples from the central nervous system (CNS) of multiple sclerosis (MS) patients. By immunofluorescence microscopy, MAb 6B9 intensely stains most or all cells in fetal rats. However, MAb 6B9 differentially stains various cell types in adult rats. Neurons, ependymal cells, and adrenal chromaffin cells are stained intensely, whereas astrocytes and oligodendrocytes are not stained. The 6B9-reactive antigen (6B9 antigen) is sensitive to periodic acid, but insensitive to treatment with protease, RNase, or hyaluronidase. Results from immunofluorescence microscopy on semithin sections and cultured neuroblastoma cells indicate that 6B9 antigen is intracellular. This is supported by immunoelectron microscopy, where labeling for 6B9 antigen appears in the cytoplasm distinct from any identifiable organelle. Further studies on 6B9 antigen should reveal its chemical nature as well as the significance of developmental changes in its distribution.     

Increased ratio of saturated to unsaturated C18 fatty acids in colonic adenocarcinoma: Implications for cryotherapy and lipid raft function

Mammalian fatty acid synthase (FASE) overexpression has been shown in a number of human malignancies including colonic adenocarcinoma. Since FASE synthesizes only saturated fatty acids, we hypothesized that cancer cells have a greater proportion of long-chain saturated fatty acids. We studied and found an unequivocal increase in saturated C18 fatty acid (stearic acid) in colonic adenocarcinoma compared to adjacent normal colonic mucosa. The increase is even more striking when measured as a ratio of stearic acid to the unsaturated C18 fatty acids (oleic acid and linoleic acid). This change in fatty acid composition of the cancer cells should significantly alter their physical and biological properties. The increase in relative proportion of saturated fatty acids should make the cancer cells more susceptible to cryodamage and measurement of fatty acid composition of cancer cells may help individualize the temperature for cryotherapy. Also, the lipid alterations may affect the structure and functions of lipid rafts, which may enable the cancer cells to affect signaling mechanisms such as those involved in cell growth and apoptosis. Dietary or therapeutic interventions targeting lipid rafts may thus be an option for cancer treatment.     

Exacerbation of Partial Seizures and Onset of Nonepileptic Myoclonus with Carbamazepine

A child had two to three generalized tonic-clonic (GTC) seizures per week unresponsive to phenobarbital (PB) and valproate (VPA). Interictal EEG demonstrated left occipital spikes. When carbamazepine (CBZ) therapy was started, he developed very frequent (4-6/day) complex partial seizures (CPS) characterized on ictal EEG by focal right temporal lobe discharges. The seizure exacerbation, which was associated with development of nonepileptic, multifocal myoclonus, resolved 24 h after CBZ was discontinued. The exacerbation occurred with therapeutic CBZ serum levels, but may have been related to the toxic levels of carbamazepine-10, 11-epoxide (CBZE).     

Genetic immunization with GPI-anchored anthrax protective antigen raises combined CD1d- and MHC II-restricted antibody responses by natural killer T cell-mediated help

Studies have demonstrated that lipid rafts ultimately regulate the endocytosis of anthrax toxin via clathrin dependent pathway. Interestingly, GPI-anchored protein rich rafts have also been shown to be transported down to the endocytic pathway to reducing late endosomes. Taking advantage of this parallelism, we tried translating the anthrax toxin natural intoxication mechanism by administering a DNA chimera that encoded protective antigen attached to a mammalian GPI-anchor sequence at its C-terminus (pGPI-PA63). We also designed a chimera that had an additional N-terminal TPA leader sequence (pTPA.GPI-PA63) with an aim to target GPI-PA63 to ER where new CD1 molecules are synthesized. Analysis of antibody titers demonstrated successful priming and potential IgG titers after the first boost. In vitro cell proliferation studies in the presence of GPI-attached PA63 peptides revealed that there was a clonal expansion of CD4⁺ NK1.1⁺ helper T cell population which rapidly produced IL-4 in response to T cell receptor ligation. These cells provided direct B cell help that aided IgG formation. Effector responses generated by NKT cells were found to be MHC II-independent and CD1d-restricted. In addition, the group pTPA.GPI-PA63 also displayed low magnitude MHC-II restricted (CD1d-independent) NKT cell and CD4⁺ T cell helper responses in response to non-GPI attached PA63 peptides which overall resulted in the heightened responses seen for this group. Importantly, DNA vaccination mediated the generation of high avidity neutralizing antibodies that mediated protection against lethal toxin challenge.     

Melatonin rhythms and pineal structure in a tropical bat, Anoura geoffroyi, that does not use photoperiod to regulate seasonal reproduction

Abstract: It has been hypothesized that pineal structure and function might differ between temperate zone and tropical species of mammals because of lower amplitudes of seasonal change in photoperiod and, in some areas, less seasonal climatic variation. Anoura geoffroyi produce a single offspring in November or December of each year on the Caribbean island of Trinidad, at 10°N latitude in the deep tropics. Previous work has shown that this population lacks reproductive responses to photoperiod, and must be enforcing seasonal breeding using a non-photoperiodic cue. Anoura geoffroyi have a minute, thin, and rod-like pineal gland. Throughout much of its length, the pineal courses irregularly within the ventrolateral wall of the great cerebral vein. This intimate relationship may have functional implications. Despite having a very small pineal gland, this species produced a nocturnal rise in serum melatonin. Serum melatonin levels in most individuals were below or near undetectable levels during the light period and rose to a peak averaging 100 pg/ml in the last third of the dark period. Our results indicate that, although the pineal gland of A. geoffroyi is extremely small, serum melatonin levels are comparable to those of other mammals.     

Essential drugs in primary health care

On September 7-8, 1988, health professionals attended a national seminar at the National Institute of Public Cooperation and Child Development in New Delhi to review policies of each government department in India that dispenses essential drugs to PHC workers. Another objective included the need to agree on what essential drugs should be distributed by the various types of PHC workers. The consensus of the group was that the different levels of health services and competence of the PHC workers should determine the basic list of PHC essential drugs. In addition, the morbidity pattern in the community, safety, effectiveness, and cost of the drugs must also determine which drugs are essential. Anganwadi workers/village health guides should all have a kit with 17 of the 75 essential drugs, such as vitamin A solution, oral rehydration solution packets, choloroquine, and chlorine tablets. In addition to the same 17 drugs, all subcenters should have in stock aspirin, metoclopramide, oral contraceptives, methergin in both tablet and injection form, and activated charcoal. Each PHC center should have all of the above and the remaining 53 drugs which include antibiotics, bronchodialators, eye drops, injections, vaccines (e.g., DPT and BCG), ointments, antileprosy drugs, and snake venom. The quantity of each drug should be based on the morbidity pattern, seasonal trend, and sickness load of the area. All PHC workers should attend inservice training where tested and effective training modules and charts in each local language are used to learn how to judiciously prescribe these drugs. Further, this essential drug program should be continuously monitored and evaluated.     

ENDOSCOPY ASSISTED REMOVAL OF FERROMAGNETIC COINS WITH NOVEL MAGNETIC INSTRUMENT

Background: Ingestion of coins is a common clinical problem in children. Many of the coins are ferromagnetic and can be retrieved with the help of a magnet. We describe the use of a novel endoscopic accessory for removing ferromagnetic coins. Material and methods: Two magnet discs of 1.5 cm diameter were joined to a 200 cm steel wire of 0.75 mm thickness with a terminal 5 cm spring. A Teflon tube (160 cm, 7 F) was used along with this instrument as a sleeve. The use of this accessory was analyzed prospectively in subjects presenting with a history of coin ingestion. The time taken for removal of coins, complications during the procedure and failure rate was noted. Effect of the magnet on cardiac rhythm was also noted during the procedure. Results: A total of 55 children (mean age 5.1 ± 2.3 years) with coin ingestion presented over a period of 1 year. Forty‐four coins were ferromagnetic. All ferromagnetic coins were removed successfully. Mean time for removal was 68 ± 22 s. No complications were encountered. Conclusion: The novel magnetic instrument is precise, safe and quick for the removal of ferromagnetic coins under direct vision.