The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Antigens of Mycobacterium tuberculosis Recognized by Antibodies during Incipient, Subclinical Tuberculosis

Serum samples obtained from human immunodeficiency virus (HIV)-infected tuberculosis (TB) patients months prior to clinical TB were used to delineate the profile of Mycobacterium tuberculosis culture filtrate proteins recognized during subclinical TB. A subset of ~12 antigens was recognized by antibodies in these serum samples. Antibodies to two of these antigens (81 [88]-kDa malate synthase [GlcB] and MPT51) were present in serum samples obtained during incipient subclinical TB in 19 (~90%) of the 21 HIV-infected TB patients tested. These antigens will be useful for devising diagnostic tests that can identify HIV-positive individuals who are at a high risk for developing clinical TB.     

Value of extracorporeal piezoelectric lithotripsy in treatment of gallstone disease

Alternative techniques were introduced in the last 20 years for the treatment of gallstones. Among these the extracorporeal shock wave lithotripsy followed by a systemic litholytic therapy represents undoubtedly the most attractive one. A group of two surgeons and two gastroenterologists has started to evaluate this treatment in April 1988, using a piezoceramic lithotryptic system (Piezolith 2300). From April 1988 to May 1989 we have treated 32 patients who fulfilled the selection criteria-symptomatic gallstone disease, 1-3 radiolucent concrements of less than 30 mm of diameter, functioning gallbladder. We noted only one pancreatitis as a complication of this treatment. The overall stonefree rate is 16% after two months, 32% after four months and 56% after six months, depending on the size and number of stones. A definitive evaluation and final conclusion will only be possible when the rate of late recurrences after this treatment will be known.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

The dissection of the rectus abdominis myocutaneous flap with complete preservation of the anterior rectus sheath.

Harvesting the rectus abdominis myocutaneous flap results in defects in both the rectus abdominis muscle and the anterior rectus sheath, which may be circumvented by dissecting a perforator flap (DIEP flap) instead. However, the latter is associated with a reduction in the number of myocutaneous perforators nourishing the flap, which has been hypothesised to lead to an increased risk of partial flap failure. We present a technical modification that maintains all the feeding perforators within the flap while fully preserving the anterior rectus sheath. The anterior rectus sheath is incised along a line connecting the perforators. A muscle cuff including all the feeding perforators was raised with the flap. This technique was used in 20 consecutive patients. Nine patients underwent free TRAM flap transfers for breast reconstruction (10 flaps), and 11 patients underwent thoracic-wall reconstruction with a superiorly based pedicled flap. The median follow-up was 11 months. One patient with a pedicled flap developed a partial failure that required surgical revision; all other flaps healed spontaneously. One patient in each subset had preoperative abdominal-wall laxity that was partly corrected after surgery; no abdominal bulging or hernia occurred in the other patients. Our results suggest that the technical modification presented here may enable the surgeon to dissect a rectus abdominis myocutaneous flap with maximal perforator-related flap perfusion and minimal donor-site morbidity. An advantage over the DIEP flap is that this technique is applicable to both free and pedicled flaps.