Profuse variceal hemorrhage as a presenting feature of pancreatic adenocarcinoma in a young non-icteric patient

Pancreatic adenocarcinoma can present with a vast spectrum of rare manifestations. It usually occurs after the age of 50 years, the peak incidence being in sixth and seventh decades. We report a previously asymptomatic subject of pancreatic adenocarcinoma who presented for the first time with massive upper gastrointestinal hemorrhage. Endoscopy revealed ruptured esophageal varices which were secondary to tumour-induced thrombosis of the portal vein. Besides the uncommon mode of presentation, the patient was unusual because of his young age. Further, he was non-icteric at the time of presentation and remained so throughout the clinical course despite having a large lesion in the head of the pancreas.     

Genotypic and phenotypic variability of 22q11.2 microduplications: An institutional experience

Duplications in the 22q11.2 region can cause 22q11.2 duplication syndrome and encompass a variety of phenotypes including developmental delays, facial abnormalities, cardiovascular defects, central nervous system delays, and other congenital abnormalities. However, the contribution of these contiguous duplicated regions to the clinical phenotypes has not been fully elucidated. In this study, we identified nine patients carrying different 22q11.2 microduplications detected by chromosomal microarray. Of these patients, seven pediatric patients presented with various clinical features including two neonate cases died shortly after birth, and two healthy adults. We examined region specific genotype–phenotype associations and found unpredictability associated with 22q11.2 duplications in these nine patients.     

Assessment of the epidemic potential of a new strain of rotavirus associated with the novel G9 serotype which caused an outbreak in the United States for the first time in the 1995-1996 season

Rotavirus causes severe morbidity in developed countries and frequent deaths (> or = 500,000 per year) in less-developed countries. Historically, four serotypes--G1, G2, G3, and G4-have predominated; they are distinguished by one of two surface neutralization antigens (VP7). However, in 1983 and 1984 we described a new rotavirus serotype, designated G9, in five children hospitalized for diarrhea in Philadelphia, Pa. G9 rotavirus was not identified again in the Western Hemisphere until it caused ca. 50% of the rotavirus disease detected in Philadelphia in the 1995-1996 season. This outbreak allowed us to question whether a rotavirus strain completely new to a well-studied community would target either very young infants or older children, cause especially severe disease, or completely displace previously extant serotypes. We observed a significant excess of G9 infections in younger infants (especially in those < 6 months old) that might be attributed to the lack of G9-specific antibodies in mothers. Of further note, six of the seven oldest patients with rotavirus diarrhea were infected with the G9 strains (not significant). However, the age distribution of children with rotavirus did not differ over a 5-year study period regardless of the infecting serotype. Patients with diarrhea associated with G9 strains did not have disease more severe than that caused by the G1, G2, or G3 serotype. G9 strains did not displace the other serotypes but were virtually completely replaced by G1 or G2 serotypes in the three subsequent rotavirus seasons. We conclude that the abrupt appearance of this novel rotavirus serotype did not present a special threat to public health in the community.     

The effect of carbon dioxide in the airways and alveoli on ventilation; a vagal reflex studied in the dog

1. The inhalation of CO(2) produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing 16-24 kg, anaesthetized with chloralose. When the ;bypass' was established pulmonary blood flow ceased, P(A, CO2) was reduced and the respiratory rate slowed. 3-10% CO(2) in O(2) could then be inhaled without change in the level of P(a, CO2) set at the oxygenator.3. The addition of CO(2) in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in O(2), given as a control, had no effect on breathing.5. The effect of raising P(a, CO2) (by increasing the concentration of CO(2) in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring CO(2)/O(2) mixtures was shown to be additive to the effect of raising P(a, CO2).7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on ;bypass', inhales low concentrations of CO(2) in O(2).     

Comparison of the chemotactic responsiveness of two fibrosarcoma subpopulations of differing malignancy.

There are several points of similarity between the processes of cancer metastasis and inflammation. In both, cells circulate in the vasculature, arrest, and cross vessel walls, thereby entering the extravascular tissues. In vitro, leukocytes and some, but not all, tumor cells exhibit chemotaxis. Since the chemotactic response of leukocytes effect their transvascular migration, we propose that chemotactic responsiveness contributes to the ability of circulating tumor cells to localize in extravascular tissues. This study was done to seek a relationship between chemotactic responsiveness of tumor cells and their behavior in vivo. Two subpopulations of cells were isolated from a methylcholanthrene-induced fibrosarcoma. The two cell lines were compared with regard to their biologic behavior in vivo and their chemotactic responsiveness in vitro. In vivo one subpopulation was highly malignant. An injection of 2.0 x 10(5) cells into the footpad of syngeneic mice led to the development of primary tumors in 87% of the animals and lung metastases in 61% of the animals with primary tumors. This line demonstrated chemotaxis to a factor that behaved similarly in gel filtration and showed immunologic reactivity similar to that of a previously described tumor cell chemotactic factor derived from the fifth component of complement. In contrast, an injection of the same number of cells from the second subpopulation of fibrosarcoma cells led to the development of primary tumors in only 12% of syngeneic mice, and lung metastases did not occur. Neither this subpopulation nor normal embryonic fibroblasts demonstrated chemotactic responsiveness. We postulate that the ability of tumor cells to respond to specific chemotactic stimuli may be one of the many unique properties which distinguish malignant from benign tumor cells. This is the first report documenting the chemotactic responsiveness of non-ascites tumors and fibrosarcomas.     

Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder

Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)_n repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)_n repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z = 1.91, p = 0.055). An excess of non-transmissions was detected for the 150 and 152 bp alleles (Z = −2.26, p = 0.023; Z = −2.20, p = 0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p = 0.011), and lower effort (p = 0.008), activation (p = 0.008) and attention (p = 0.01) cluster scores. We did not replicate association findings in the case–control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)_n repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.     

Aspiration cytology of ameloblastic fibroma: a diagnostic challenge

Ameloblastic fibroma of the jaw is a rare, benign mixed odontogenic tumor, having little tendency for local invasion and a low recurrence rate. Cytologic distinction from ameloblastoma, ameloblastic fibrosarcoma, and intraosseous adenoid cystic carcinoma is necessary, in view of the different biologic behavior. A painful, slow-growing swelling of the jaw in a 5-yr-old child clinicoradiologically considered as a benign cystic lesion was aspirated. Sheets of small monomorphic epithelial cells with peripheral palisading by columnar cells were seen on cytology smears. The striking feature was central hyaline globules in some tubules. A cytologic possibility of adenomatoid odontogenic tumor was suggested. Histopathology, however, confirmed it to be an ameloblastic fibroma.     

Effects of prednisolone treatment on cytokine expression in patients with leprosy type 1 reactions

Leprosy type 1 reactions (T1R) are due to increased cell-mediated immunity and result in localized tissue damage. The anti-inflammatory drug prednisolone is used for treatment, but there is little good in vivo data on the molecular actions of prednisolone. We investigated the effect of prednisolone treatment on tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-10, and transforming growth factor beta1 (TGF-beta1) mRNA and protein expression in blood and skin biopsies from 30 patients with T1R in India. After 1 month of prednisolone treatment the sizes of the skin granulomas were reduced, as were the grades of cells positive for TNF-alpha and IL-10 in skin lesions. Increased production of TGF-beta1 was seen in skin lesions after 6 months of prednisolone treatment. Expression of mRNA for TNF-alpha, IL-1beta, and TGF-beta1 was reduced, whereas no change in IL-10 mRNA expression was detected during treatment. The circulating cytokine profiles were similar in patients with and without T1R, and prednisolone treatment had no detectable effects on cytokine expression in the blood. The data emphasize the compartmentalization of pathology in T1R and the importance of the immune response in the skin. Clinical improvement and cytokine expression were compared. Surprisingly, patients with improved skin and nerve function and patients with nonimproved skin and nerve function had similar cytokine profiles, suggesting that clinical improvement is not directly mediated by the cytokines studied here. This in vivo well-controlled study of the immunosuppressive effects of prednisolone showed that the drug does not switch off cytokine responses effectively.     

A prospective randomized,double-blinded,placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy

BACKGROUND: Vaginal misoprostol has been shown to be an effective single agent for medical abortion. This randomized, double-blinded, placebo-controlled trial compared a regimen of mifepristone and misoprostol with misoprostol alone for termination of early pregnancy. METHODS: 250 women with gestations < or = 56 days were randomized by a random number table to receive either 200 mg mifepristone orally or placebo followed 48 h later by 800 microg vaginal misoprostol. Administration of misoprostol was repeated every 24 h up to three doses if abortion failed to occur. Abortion success was defined as complete abortion without the use of surgical aspiration. RESULTS: Successful medical abortions occurred in 114 out of 119 subjects (95.7%) after mifepristone followed by vaginal misoprostol. In all, 110 out of 125 subjects (88.0%) successfully aborted after placebo and vaginal misoprostol. The higher success rate of complete abortion with the mifepristone and misoprostol regimen was statistically significant compared with the placebo and misoprostol regimen (P < 0.05). CONCLUSIONS: A regimen of mifepristone and misoprostol was significantly more effective for termination of pregnancies < or = 56 days than misoprostol alone. The 88% efficacy obtained with vaginal misoprostol alone may be clinically acceptable when mifepristone is not available.     

Bone growth in zebrafish fins occurs via multiple pulses of cell proliferation.

Fin length in the zebrafish is achieved by the distal addition of bony segments of the correct length. Genetic and molecular data provided evidence that segment growth uses a single pulse of growth, followed by a period of stasis. Examination of cell proliferation during segment growth was predicted to expose a graphical model consistent with a single burst of cell division (e.g., constant, parabolic, or exponential decay) during the lengthening of the distal-most segment. Cell proliferation was detected either by labeling animals with bromodeoxyuridine (during S-phase) or monitoring histone3-phosphate (mitosis). Results from both methods revealed that the number of proliferating cells fluctuates in apparent pulses as a segment grows (i.e., during the growth phase). Thus, rather than segment size being the result of a single burst of proliferation, it appears that segment growth is the result of several pulses of cell division that occur approximately every 60 microns (average segment length approximately 250 microns). These results indicate that segment lengthening requires multiple pulses of cell proliferation.