Relative contribution of angiotensin II, bradykinin, and prostaglandins to the renal effects of converting enzyme inhibition in rats after chronic myocardial infarction

The brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblasts seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs (approximately 300 bp) corresponding to the 3' ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones.     

Beckwith-Wiedemann syndrome: antenatal diagnosis

The Beckwith-Wiedemann syndrome is an unusual complex with variable features. The major findings include abdominal wall defects, macroglossia and visceromegaly. These features should be amenable to antenatal ultrasound detection. Only a few such cases have been reported to date. Antenatal diagnosis allows optimum perinatal care. Hypoglycaemia in the neonatal period is common in these babies and requires early detection and appropriate management to prevent long-term intellectual complications. We present a case where the diagnosis was suggested prior to delivery.     

The efficacy of diaspirin crosslinked hemoglobin solution resuscitation in a model of uncontrolled hemorrhage

Controversy exists whether early aggressive fluid therapy in the setting of uncontrolled hemorrhage worsens outcome by increasing blood loss from injured vessels. Since diaspirin crosslinked hemoglobin (DCLHb) is a vasoactive, oxygen-carrying solution, we compared the effects of DCLHb with other resuscitative fluids on blood loss, hemodynamics, and tissue oxygen delivery in a model of uncontrolled hemorrhage. Anesthetized rats (250-350 g) were subjected to a 50% tail transection and resuscitated 15 minutes later with 1:1 DCLHb, 3:1 lactated Ringer's solution (LR), 1:1 hypertonic saline (7.5% HTS), or 1:1 human serum albumin (8.3% HSA) based on initial volume of blood loss (average 4.7 +/- 0.3 mL/kg). An unresuscitated group served as a control. Cumulative blood loss was measured at 5 hours postresuscitation. By 15 minutes after tail transection, mean arterial pressure (MAP) decreased 19.2 +/- 3.8 mm Hg from the baseline value (102 +/- 5 mm Hg). The DCLHb solution restored and maintained MAP and subcutaneous tissue oxygen tension at baseline values better than all other resuscitative fluids. Although blood loss in DCLHb-treated animals was greater than in unresuscitated animals, it was no different from other resuscitative fluids and less than with HSA. There was no difference in 24-hour survival between all treatment groups. In conclusion, DCLHb elevates MAP but does not exacerbate blood loss or compromise tissue oxygen delivery compared with other resuscitative fluids in this model of uncontrolled hemorrhage.     

Percutaneous nephroscopy in the diagnosis of renal pelvic filling defect: a report of two cases

Diisoeugenol inhibited the platelet aggregation and ATP release of rabbit platelets caused by ADP, arachidonic acid, platelet-activating factor (PAF), collagen and thrombin. Prolongation of the incubation time of platelets with diisoeugenol did not cause further inhibition and the aggregability of platelets could not be restored after washing. In human platelet-rich plasma, diisoeugenol inhibited the biphasic aggregation and ATP release induced by adrenaline and ADP in a concentration-dependent manner. Thromboxane B2 formation caused by arachidonic acid, collagen and thrombin was markedly inhibited by diisoeugenol in a concentration-dependent manner. Diisoeugenol also inhibited the formation of inositol monophosphate caused by collagen, PAF and thrombin. The cAMP level of washed platelets was not changed by diisoeugenol. It is concluded that the antiplatelet effect of diisoeugenol is due to the inhibition of thromboxane formation and phosphoinositides breakdown.     

A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light

A mouse gene, mper1, having all the properties expected of a circadian clock gene, was reported recently. This gene is expressed in a circadian pattern in the suprachiasmatic nucleus (SCN). mper1 maintains this pattern of circadian expression in constant darkness and can be entrained to a new light/dark cycle. Here we report the isolation of a second mammalian gene, mper2, which also has these properties and greater homology to Drosophila period. Expression of mper1 and mper2 is overlapping but asynchronous by 4 hr. mper1, unlike period and mper2, is expressed rapidly after exposure to light at CT22. It appears that mper1 is the pacemaker component which responds to light and thus mediates photic entrainment.     

Comparison of six respirator fit-test methods with an actual measurement of exposure in a simulated health care environment: Part I--Protocol development

Quantitative fit tests (QNFT) have been assumed to be predictive of the protection respirators would provide to a wearer in the workplace. Workplace studies have consistently found no correlation between quantitative fit factors and workplace protection factors. This article is the first in a series of three describing a study designed to compare the fit factors from six QNFT methods against the actual dose of 1,1,2 trichloro-1,2,2 trifluoroethane (Freon-113) received under the same laboratory conditions. Five preliminary studies conducted to develop the protocol to assess the respirator wearer's dose through end-exhaled air analysis are described in this article: (1) chamber characterization, (2) end-exhaled air sampling, (3) skin absorption testing, (4) pharmacokinetic modeling, and (5) subject characterization. It was established that the concentration of corn oil aerosol and Freon-113 could be generated simultaneously in the chamber. It was ascertained that the optimum time to sample the exhaled breath was 30 minutes after the subject exited the chamber. It was also found that in a chamber concentration of 500 ppm, without any respiratory exposure, Freon-113 was still present in the end-exhaled air. This was attributed to skin absorption. The end-exhaled air of subjects exposed to 0.5, 3, 5, 25, 50, and 100 ppm (30 minute time-weighted average) of Freon-113 was evaluated at 30 minutes postexposure. This characterization was then used to predict the actual dose of Freon-113 received during the method comparison and validation testing to be described in subsequent articles.     

Renal replacement therapy in multiple myeloma and systemic amyloidosis

Renal failure frequently complicates both multiple myeloma and systemic amyloidosis. Renal replacement therapy (RRT) may be poorly tolerated and its role in such patients is not clearly defined. Of fifty patients (26 males and 24 females) referred to a single centre because of renal failure associated with multiple myeloma or systemic amyloidosis 37 progressed to end-stage renal failure and 30 of these patients received RRT. Nine patients have been treated by CAPD, 13 by haemodialysis, and 8 patients have required both forms of dialysis. Overall one year and two year survival rates were 66% and 57% respectively. The median duration on RRT was 7.5 months (range 1-96 months) with a 51% one year, and a 46% two year survival rate. Of 7 patients with amyloidosis who underwent renal transplantation, 3 died within 6 months of transplantation. Undiagnosed cardiac involvement contributed to this early mortality. We conclude that renal replacement therapy is appropriate for some patients with multiple myeloma and systemic amyloidosis who develop endstage renal failure. Careful assessment and selection of patients is necessary prior to renal transplantation.