Bone disorders following total gastrectomy

Bone disorders following gastrectomy were studied by measuring absolute and relative bone mineral density of the Wards triangle, serum 1,25-(OH)₂-D, alkaline phosphatase, and total serum calcium. The subjects were 20 males who had undergone total gastrectomy not more than three months previously (group A₁). Seventeen of these patients were reviewed three years later (group A₂). Absolute and relative bone density were significantly lower in group A₂ than in A₁ (0.52 ± 0.011 g/cm² versus 0.6 ± 0.014 g/cm²,P<0.01 and 85.5 ± 1.4% age-matched control versus 95 ± 1.3%,P<0.01). 1,25-(OH)₂-D was significantly lower in group A₂ than in group A₁ (14.3 ± 0.97 pg/ml versus 20.6 ± 1.02 pg/ml,P<0.01). There was no difference in alkaline phosphatase and calcium serum concentration. The mean weight loss was 6.26 ± 0.57% over the follow-up period, and weight loss correlated with absolute and relative bone density (r=–0.74,P<0.01). There was a positive correlation between 1,25-(OH)₂-D and absolute or relative bone density (r=0.67,r=0.62 andP<0.01). These data suggest that bone density decrease has already occurred three years after total gastrectomy and is positively correlated to 1,25-(OH)₂-D deficiency. As no differences in serum alkaline phosphatase and serum calcium concentration were found, these factors are of little value for the early detection of postgastrectomy bone disorders, whereas weight loss is a valuable screening parameter.     

Cor pulmonale caused by recurrent pulmonary emboli

A 53-year-old black man developed femoral thrombophlebitis in 1983 following a Harrington nail implantation in his first lumbar vertebral region. There was evidence of pulmonary embolization at that time and recurrently until he developed ventricular fibrillation and died in 1987. The terminal event followed a hypotensive episode during the course of a right ventricular catheterization. Autopsy confirmed the clinical impression that he had multiple recurrent thromboemboli to his lungs. After several years of embolization, the pulmonary arterial circulation was sufficiently occluded to result in pulmonary hypertension. Cor pulmonale was produced, with congestive heart failure leading to a progressively downhill course in the 4 months before his death.     

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

A model for the antagonist binding site on the adenosine A1 receptor, based on steric, electrostatic, and hydrophobic properties

With the aid of molecular modeling, both adenosine and adenosine A1 receptor antagonists belonging to various chemical classes were compared with respect to their minimum-energy conformations and molecular electrostatic potentials, as computed by the semiempirical molecular orbital program MOPAC. Distinct steric and electrostatic similarities between adenosine and the prototypic adenosine antagonist theophylline are evident when both compounds are superimposed, with theophylline in a so-called flipped orientation. Similar patterns were found for all other A1 antagonists investigated in this study. A model for the antagonist binding site on the adenosine A1 receptor, based on steric, electrostatic, and hydrophobic properties contributing to potency, is proposed.