Dysregulation of blood lymphocyte subsets and natural killer cells in schistosomal liver cirrhosis and hepatocellular carcinoma

Immunological factors are important in the pathogenesis of a wide spectrum of hepatobiliary diseases. Using flow cytometry, we determined the changes in lymphocyte subsets and natural killer cells in 123 individuals (81 patients with liver disease and 42 healthy volunteers). The liver diseases included periportal fibrosis (PPF, 10 patients), liver cirrhosis (LC, 31 patients), and hepatocellular carcinoma (HCC, 40 patients). Schistosomiasis and viral hepatitis B and C were the putative etiological agents of liver diseases. Immunophenotyping by indirect immunofluorescence was conducted using monoclonal antibodies to CD3 (T-lymphocytes), CD4 (helper/inducer T-cells), CD8 (suppressor/cytotoxic T-cells), and CD57 (natural killer cells) cell surface markers. Immunophenotyping of PPF patients showed no significant changes in all markers compared with the healthy controls. However, there was a significant decrease ( P<0.01) in CD3 and CD4 T-cells, and a highly significant increase ( P<0.001) in CD57 T-cells in patients with LC or HCC. In addition, LC and HCC patients showed no significant change in CD8 T-cells compared with controls. In conclusion, the progression of liver diseases is associated with a dysregulation of cellular immune responses. T-lymphocytes and natural killer cells may play a role in the immunopathogenesis of liver cirrhosis and HCC.     

Extradural Extranasal Combined Transmaxillary Transsphenoidal Approach to the Cavernous Sinus: A Minimally Invasive Microsurgical Model

The authors have previously described an extradural transmaxillary approach to the anterior compartment of the cavernous sinus. In an effort to expand the surgical access to that area without necessitating a craniotomy or wide transfacial dissection, they present a modification of the transmaxillary approach to the sellar region and cavernous sinus. Methods: The approach was developed on 12 fresh and 12 embalmed cadaveric specimen, and 2 dry skulls. The initial sublabial incision is followed by a maxillotomy to expose the course of the infraorbital nerve (terminal branch of maxillary branch of the trigeminal nerve) on the roof of the maxillary sinus. The route of the infraorbital nerve is traced to the pterygopalatine fossa as a guide to the foramen rotundum. Superomedial drilling of the foramen rotundum is then performed to reveal the contents of the superior orbital fissure. After the nerves are safely identified in the superior orbital fissure, medial enlargement of the window into the cavernous sinus is made possible by drilling the lateral and posterior wall and septum of the sphenoid sinus. Results: The combined transmaxillary transsphenoidal approach offers an excellent exposure of the sellar and infrasellar region. The approach offers clear visualization of the ipsilateral loop of the carotid artery, the pituitary fossa, and the cranial nerves of the ipsilateral cavernous sinus. Mean operative reach is 38 mm from the posterior wall of the maxillary sinus to the ipsilateral carotid loop and 56 mm to the contralateral loop. The width of the operative window is 26 mm at the base within the cavernous sinus. Conclusion: The model offers a minimally invasive approach that avoids the need for craniotomy or violating the nasal cavity. It may be safely employed to access vascular as well as invasive lesions of the sellar and infrasellar region. The approach offers excellent visualization of the ipsilateral intracavernous carotid artery with both proximal and distal control, as well as cranial nerves III, IV, VI, V2, the hypophyseal region, and the medial aspect of the contralateral cavernous sinus.     

Dynamic assessment of the electrocardiographic QT interval during citrate infusion in healthy volunteers.

OBJECTIVE--To investigate changes in the electrocardiographic QT interval during rapidly induced, sustained hypocalcaemia in healthy volunteers. DESIGN--Serial rate corrected QT measurements were made during and after a variable rate trisodium citrate infusion designed to "clamp" the whole blood ionised calcium concentration 0.20 mmol/l below baseline for 120 min. SUBJECTS--12 healthy teetotallers aged 19- 36 years who were not receiving medication known to influence calcium homoeostasis. MAIN OUTCOME MEASURES--Whole blood ionised calcium concentration and QaTc intervals (onset of the Q wave to T wave apex divided by the square root of the RR interval). RESULTS--Mean (SD) ionised calcium concentration decreased from 1.18 (0.03) mmol/l preinfusion to values close to target (0.98 mmol/l) between 10 and 120 min. The QaTc interval lengthened from a baseline of 0.309 (0.021) to a maximum 0.343 (0.024) s0.5 at 10 min before returning to a stable level from 15 to 120 min (0.334 (0.023) and 0.330 (0.023) s0.5 respectively). The change from baseline of both variables expressed as a ratio (delta QaTc/ delta [Ca2+]) was greater during rapid induction of hypocalcaemia (at 5 and 10 min) than at other times during and after the infusion (P < 0.02). CONCLUSIONS--The disproportionate prolongation of QaTc interval during prompt induction of hypocalcaemia suggests rate dependency which can be represented by a hysteresis relation between (ionised calcium, QaTc) coordinates. This finding may have clinical implications.     

Reproductive toxicity and toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin

Possible effects on the next generation after long-term exposure (subcutaneous administration) of male rats to very high doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied. Two dose regimes were applied: TCDD-25 (initial dose: 25 g/kg body wt; maintenance dose: 5 g/kg body wt, once weekly) and TCDD-75 (initial dose: 75 g/kg body wt; maintenance dose: 15 g/kg body wt). Male rats were treated for 10 weeks before mating and then throughout the entire 12 week mating period. They were mated to unexposed virgin females. One group of pregnant females was used for teratological evaluations, and another group was allowed to deliver. No significant differences were observed in the number of implantations or fetuses per litter, and resorption rate, and fetal weight between the controls and TCDD-treated groups. No gross-structural anomalies occurred in any of the fetuses sired by TCDD-treated males. In the TCDD-25 group an increased frequency of two types of variations was observed which also occur in controls: incompletely ossified fingers (TCDD-25=5.1%, controls=2.6%), and incompletely ossified ossa zygomatica (TCDD-25=1.8%, controls=0.5%). In the TCDD-25 group a slight but statistically significant increase was observed in the rate of stillbirths (TCDD-25=1.3%, controls=0.1%), apparently due to an unusually low frequency occurring in the controls (overall historical controls=0.6%). There was no difference in postnatal mortality (TCDD-25=1.3%, controls=1.3%). Taken together, despite the very high doses of TCDD used, the data do not provide evidence for biologically significant paternally-mediated developmental toxicity in the fetuses and newborn.     

Infrapopliteal prosthetic graft patency by use of the distal adjunctive arteriovenous fistula

From November 1979 through December 1989, 210 distal arteriovenous fistulas were constructed as adjuncts to tibial and peroneal vascular reconstructive procedures in 203 patients threatened with limb loss. Two-year cumulative patency rates were calculated by grouping patients on the basis of changing indications in sequential time periods: group 1 (n = 61): 1979 to 1983, 18%; group 2 (n = 80): 1983 to 1986, 33%; group 3 (n = 69): 1986 to 1989, 44%. Although the therapeutic results observed in these groups are not statistically comparable, they show a perceptible trend. Postoperative arteriography showed that flow is prograde in the distal vessels beyond the distal arteriovenous fistula. Graft surveillance by duplex ultrasonography also confirmed that flow in the distal arteries is prograde and that "steal" does not occur. Peak systolic velocity (174 +/- 38 cm/sec) and mean velocity (92 +/- 23) flow rates are increased in grafts with patent distal arteriovenous fistulas compared to those bypasses with closed distal arteriovenous fistulas (p less than 0.01). There were no differences in the flow measurements for the arteries beyond the distal anastomoses and distal arteriovenous fistulas, confirming the prograde nature of the distal flow. In 22 patients analysis of graft and fistula patency by duplex sonography showed that one fourth of all grafts were patent without fistulas at 1 and 2 years after operation. Alternatively, 68% of patent grafts at 1 year had patent fistulas and 58% had patent fistulas at 2 years. We conclude that the distal arteriovenous fistula will increase graft flow and simultaneously prevent distal arterial overload without causing "steal." This technique should be considered whenever a prosthetic graft is necessary for crural reconstruction and only in selected instances of revascularization with autologous veins.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.