A complex variation in the superficial palmar arch.

In this article we describe a unique and complex variation in the arterial pattern of the left hand of a female cadaver. The following variations were found in this case: a) persistent median artery of the palmar type, terminating in the hand as the princeps pollicis and radialis indicis arteries; b) the ulnar artery giving only two common palmar digital arteries; c) the second digital palmar artery without division into two digital branches and instead supplying only the radial side of the ring finger; d) absence of the first common digital artery with the contiguous sides of the second web space supplied by the first palmar metacarpal artery from the deep palmar arch; e) early bifurcation of the median nerve proximal to the flexor retinaculum.

Leukemia cells and the cytokine network.

The cytokine network plays an important role in the growth and differentiation of normal and leukemic cells. Stimulation of this network, which has positive and negative regulators, results in the induction or inhibition of certain hematopoietic events. A cytokine can have multiple effects on various cell types, and combinations of cytokines with each other or with other exogenous substances produce more pronounced effects than any cytokine or agent individually. The mechanisms by which cytokines affect normal and leukemic cell growth and viability may vary depending on the target cell or the cytokine(s) in question. Diseases such as leukemia may result from abnormalities in the cytokine network or their receptors. Cytokines play a major role in leukemogenesis. Normally, hematopoietic cells require certain cytokines for their viability and growth. When the viability factors are withdrawn, apoptotic cell death naturally occurs. Prevention of programmed cell death by the abnormal production of a cytokine may release the cell from normal growth control leading to malignant transformation. Disregulation of genes for hematopoietic growth factors and their receptors may be one of the events that leads to leukemogenesis through an aberrant autocrine growth mechanism. However, cytokines have been used as therapeutic agents in various ways. Differentiation therapy has been widely investigated and proven effective in certain types of cancer. Gene therapy, where the cytokine cDNA is used to reduce tumorigenicity and/or increase immunogenicity is promising. Another kind of therapy using alkylated growth factors has been under focus. This review summarizes the actions and interactions of cytokines that are related to leukemic cell viability and growth. The use of cytokines as therapeutic agents is also discussed.

Attitudes and reactions of Arab medical students to the dissecting room.

A questionnaire on the emotional and psychological reactions of Arab medical students to the dissecting room (DR) was distributed to 272 students in four successive pre-clinical and clinical years in the same academic year (1993-1994) at Sultan Qaboos University (SQU) Medical College; 205 students responded. Varying degrees of fear on first entering the DR was reported by 46%. The most frequent reactions were recurring visual images of cadavers (total 38%) and temporary loss of appetite (total 22.5%). Students' reactions were most commonly elicited by the smell of the DR (total 91%) and by fear of infection (total 62%). The most frequent method of coping with such fears was by rationalization (total 65%). Significant gender differences (P < 0.05) were found concerning all aspects of the DR experience. Female students showed higher levels of fear, reported stronger physical and behavioral reactions, were more disturbed by certain stimuli in the DR, and used certain coping methods more frequently than their male peers. The need for appropriate psychological preparation of students before studying human cadaveric anatomy is discussed.

Effect of blood substitute, recombinant hemoglobin, on in vivo hematopoietic recovery from AZT toxicity.

We determined the in vivo ability of infused human recombinant hemoglobin 1.1 (hr-Hb) and erythropoietin to rescue the hematopoietic activity from the suppressive effects of AZT in normal and in a murine model of AIDS (MAIDS) mice. Mice were fed with AZT for 8 weeks with or without treatment in the last 4 weeks by administering various concentrations of hr-Hb and/or erythropoietin (Epo). Blood parameters, body weight (BW) and erythroid burst-forming units (BFU-E) for all mice were determined. AZT-treated normal and MAIDS mice showed a significant decrease in hematocrit (64 and 78.1%), hemoglobin (27.2 and 45.5%), BW (17.5 and 35.5%), number of white (66.9 and 42.1%) and red blood cells (65.5 and 38%), and the number of BFU-E (73 and 59%), whereas the AZT-treated normal and MAIDS mice that received hr-Hb (5 mg/kg BW/day) and/or Epo (2 U/mouse/day) showed significant alleviation of AZT cytotoxicity. This was evident by the recovery in all blood indices examined, the number of BFU-E and the BW of mice treated. BFU-E recovery in MAIDS (97%) was greater than that in normal mice (63%) as compared to their controls. hr-Hb produced a similar response as the combination, however recovery was slightly better with the latter in some hematological parameters. Higher concentrations of hr-Hb (10-15 mg) did not result in a more significant increase in most blood indices. Our results indicate that infusion with hr-Hb can alleviate AZT toxicity in normal and in immunodeficient mice, and that hr-Hb may be clinically useful in preventing severe bone marrow depression brought about by various drugs or agents such as AZT.

The role of the diaphragm in lymphatic absorption from the peritoneal cavity.

Lymphatics in the diaphragm form a specialised system draining fluid from the peritoneal cavity and returning it to the vascular system. Fluid enters subperitoneal lymphatic lacunae, between muscle fibres of the diaphragm, the lacunae being separated from the peritoneal cavity by a barrier comprising, successively, lymphatic endothelium, a layer of collagenous fibres, a thin fenestrated layer of elastic tissue, and the peritoneal mesothelium. To reach the lacunae, peritoneal fluid passes through stomata located between cuboidal mesothelial cells of the lacunar roof. Whilst the distribution of mesothelial stomata and subjacent lymphatic lacunae varies in different species, stomata appear to be exclusive to the diaphragm and may serve as the main drainage channels for absorption from the peritoneal cavity. Clinically, they may provide escape for tumour cells, pathogens and toxins from the peritoneal cavity. They could provide access for blood transfusions, for intraperitoneal chemotherapy to treat malignancies, and for peritoneal dialysis in treating chronic renal failure. From the lacunae, fluid traverses the diaphragm via intrinsic lymphatics to reach collecting lymphatics beneath the diaphragmatic pleura. Both intrinsic and collecting lymphatics contain valves. The collecting lymphatics drain principally into retrosternal (parasternal) lymphatic trunks that carry lymph to the great veins after it filters through mediastinal lymph nodes.

Assessment of basic medical sciences in an integrated systems-based curriculum.

Basic medical sciences at Sultan Qaboos University (SQU) are taught in a systems-based curriculum. During the development of the courses different formats have been used for the written examinations and also different types of questions. This paper compares students' performance in relation to examination format and to types of questions used. The formats were non-coordinated (NCAs), each discipline having a separate paper; coordinated (CAs), questions from various disciplines being given in the same paper but with separate sections for each discipline; and integrated assessments (IAs), questions being grouped under structure, function, and problem-based integrated long essays. The types of questions used were multiple choice (MCQs), short essays (SEQs), and structured integrated long essays (SILEQs). Students performed better in SEQs than in MCQs. Our analyses also show that SILEQs measure skills similar to those of MCQs and SEQs combined. Students performed best in NCAs. In CAs, students concentrated on those disciplines carrying most weight in the final grade. Currently we use IAs consisting of two parts: part I, comprising MCQs and SEQs, and part II, comprising SILEQs. To date, students are performing better in part II than in part I. We suggest that it is prudent to use different types of questions to measure students' knowledge and skills when IAs are used for systems-based courses.

Modulation of growth supportive and oncogenic properties of murine leukemia cells.

A leukemoid reaction occurs after inoculation of L1210 leukemic cells into recipient mice and the degree of granulocytosis is correlated with tumor progression. It was found that the sera of leukemic mice contained elevated levels of colony stimulating activity (CSA) when compared with normal mouse sera. Media conditioned by L1210 cells in vitro (L1210-CM) contained CSA which stimulated normal bone marrow myeloid colony growth and an auto-stimulatory activity (ASA) which stimulated L1210 cell proliferation. We studied the effects of trans-retinoic acid (RA) and 1,25 dihydroxyvitamin D3 (VD3) on the production of growth substances by L1210 cells. When L1210-CM was prepared in the presence of RA and VD3, the CSA and ASA were markedly inhibited. A combination of the two agents was more effective than either agent. Mice inoculated with 1 x 10(5) L1210 suspension culture cells treated with either agent or both combined survived significantly longer than controls. Mice inoculated with L1210 cells treated with the two agents combined survived longest. By using antibodies, preliminary analysis of growth substances generated in L1210-CM showed that it contains primarily GM-CSF and M-CSF-like activities which were distinct from ASA. Combination antibody titer assays revealed that ASA was not significantly inhibited with anti-GM-CSF and anti-M-CSF antibodies, while CSA was inhibited by between 61 and 84%. We conclude that RA and VD3 synergistically inhibit the release of growth-enhancing substances by L1210 cells which may reduce the growth advantage of leukemic cells and the resulting leukocytosis in lymphocytic leukemia.

Hemopoietic recovery from AZT toxicity with recombinant hemoglobin in a murine model of AIDS.

We studied the toxic effects of azidothymidine (AZT) on the hemopoietic colony growth (CFU-E, BFU-E and CFU-GM) of bone marrow in a murine model of AIDS (MAIDS). A sparing effect by recombinant hemoglobin (r-Hb) on AZT suppression of MAIDS bone marrow was found when 10 microM of r-Hb was included in bone marrow cultures. The AZT toxicity dose response curve showed that at a concentration of 0.1 microM, AZT inhibited CFU-E by 66%, BFU-E by 55% and CFU-GM by 67%. The addition of r-Hb (10 microM) to AZT-treated cultures stimulated CFU-E, BFU-E and CFU-GM by 89, 125 and 160%, respectively, as compared with AZT-treated (control). The addition of r-Hb to non AZT-treated cultures showed further stimulation of CFU-E, BFU-E and CFU-GM to 100, 160 and 187% of the control, respectively. These results indicate that exogenous r-Hb reverses AZT-induced hemopoietic toxicity and may prove to be useful in ameliorating AZT toxicity in immunosuppressive diseases.

Differential induction of heme oxygenase in the hepatocarcinoma cell line (Hep3B) by environmental agents.

In situ hybridization and Northern analysis of heme oxygenase (HO) mRNA was used to determine the induction and expression of HO by various environmental agents. Exposure of Hep3B cells to hemin (10 microM) for as little as 5 min resulted in significant production of HO transcripts and mRNA expression as seen by in situ hybridization. We followed the pattern of HO transcript accumulation by heme and results indicate that the peak of induction of HO by heme was reached between 10 and 20 minutes. Other metalloporphyrins were all effective in inducing HO mRNA after 1 h exposure. On the other hand, CoCl2 caused accumulation of HO mRNA at a later time than seen with the metalloporphyrins. However, lipopolysaccharide (LPS) gave a more immediate effect on HO induction which was somewhat similar to heme in its time course. Direct measurements of HO activity revealed that enzyme activity could be detected after about 20 min exposure to hemin, and this activity was inhibited by tin protoporphyrin (SnPP). The different pattern of HO mRNA induction by LPS as contrasted with CoCl2 suggests that LPS may act through a different translational factor, or stimulate free radical formation and the subsequent release of heme and induction of HO. These results indicate that heme causes accumulation of HO mRNA by a different mechanism than that of CoCl2. Finally, LPS shares a concomitant effect on induction of HO as an acute phase reactant type protein.

Abolition of L1210 clonogeneticy and G1 arrest by retinoic acid and 1,25-dihydroxyvitamin D3.

Results from this study demonstrate that L1210 lymphocytic leukemia cells generate tumor cell colonies in plasma clot culture, and that the cells can be maintained in suspension cultures for 3 days without a loss in viability or clonogeneticy. Additions of 10(-5)-10(-8) M retinoic acid (RA) or 1,25-dihydroxyvitamin D3 (1,25VD3) to suspension cultures had no effect on cell viability. However, there was an increase in cellular adherence, nuclear chromatin condensation and a depression of clonogenic potential by 99-25%. Flow cytometry analysis of 3-day suspension cultures revealed that both RA or 1,25VD3 promoted an accumulation of cells in G1-phase, with 1,25VD3 being the most effective. For example, treatment with 10(-5) M 1,25VD3 yielded a 76.7% G1-phase accumulation as contrasted with 36.3% for controls, and associated with this G1-shift was a 97% loss in clonogeneticy. Treatment with RA gave a slightly less G1-phase accumulation (64%), which was associated with a 74% loss in clonogeneticy. It is suggested that RA and 1,25VD3 exert their cell cycle and anti-tumor effects by modulating cellular events or metabolism, or by promoting the accumulation of a quiescent cell population.