Supportive housing: a consumer evaluation study.

The current debate about how to provide housing for persons with persistent psychiatric disabilities should be informed by empirical information from a variety of sources. Data from a study of 17 residents discharged from Regeneration House Inc., illustrates the value of consumer perceptions in the evaluation of supportive housing. Extensive exploration of the positive and negative aspects of living in a group home from the perspective of experienced residents provides useful input for programme planning. The implications of the findings for the individual programme and the wider field are discussed.     

Mechanism of renal lead-binding protein reversal of delta-aminolevulinic acid dehydratase inhibition by lead

The bioavailability of lead in kidney is mediated in part by binding to endogenous high-affinity cytosolic lead-binding proteins (PbBP), which are not detectable in liver. Addition of semipurified 11,500 dalton PbBP to liver delta-aminolevulinic acid dehydratase (ALAD) reaction mixtures reverses inhibition of this enzyme by lead and thus provides an explanation for the relative insensitivity of renal ALAD to lead inhibition in vivo and in vitro. This effect results in part from a marked increase in binding of 203Pb to the PbBP relative to control liver cytosol (no PbBP) as demonstrated by Sephadex G-150 gel filtration chromatography. Zinc is known to activate ALAD and is an endogenous component of the PbBP fraction (6 microM in reaction mixtures). Zinc activated hepatic and renal ALAD over a range of 1.5 to 50 microM and also reversed the IC50 lead-inhibited activity. Studies of zinc release and/or displacement from PbBP under ALAD assay conditions (37 degrees C, + glutathione, pH 6.8) were conducted utilizing Sephadex G-25 chromatography. Fifteen to twenty-five percent of the zinc in the PbBP fraction was released, and this value was not markedly influenced by addition of IC50 lead, temperature (4 degrees C) or absence of glutathione; however, zinc release was primarily dependent upon the pH of the reaction mixture. These data indicate that the PbBP fraction attenuates lead inhibition of ALAD in vitro both by chelating lead and apparently serving as a zinc donor for this enzyme under optimal conditions of the ALAD assay.     

Antihypertensive and renal vasodilator effect of diltiazem in DOCA-salt hypertensive dog

We studied the effect of an intravenous (i.v.) infusion of diltiazem (15 micrograms/kg/min) given for 1 week on several cardiovascular parameters, renal blood flow, and electrolyte and urinary excretion in chronically instrumented DOCA-salt hypertensive dogs. On the first recording session, 24 h after diltiazem infusion was started, arterial blood pressure was decreased and renal blood flow was increased by 36%. Thereafter, the blood pressure reached a normotensive level and remained at that level for the duration of the infusion in all but one dog in which the dose had to be increased on day 7. Renal blood flow was increased for 3 days and then tended to return toward control at the end of the infusion period. An increase in urine output was seen during the period of drug infusion, but no increase in sodium excretion was detected. Pressor and renal blood flow responses to norepinephrine (NE), phenylephrine, and angiotensin II were evoked before and on the last day of the diltiazem infusion. The decreases in renal blood flow produced by all three agonists and the pressor response to NE were reduced by diltiazem. These results indicate that this calcium entry blocker can reestablish blood pressure to a normotensive level in DOCA-salt--treated dogs, but that the renal vasodilator effect accompanying the blood pressure decrease is not consistently sustained.     

Three patients with structurally abnormal X chromosomes, each with Xq13 breakpoints and a history of idiopathic acquired sideroblastic anemia

Structural abnormalities of the X chromosome are rarely found in neoplastic disorders. We describe three patients with a history of idiopathic acquired sideroblastic anemia (IASA); each one had an abnormal clone of cells in the bone marrow, characterized by a structurally abnormal X chromosome. In two of these patients, the predominant karyotype was 47,X,2idic(X)(q13); in the other patient, it was 46,X,t(X;11)(q13;p15). Inasmuch as all three of these cases involved chromosome band Xq13, as did two previously published cases, we suggest that band Xq13 may be more prone to structural rearrangement than other X chromosome bands in hematologic disorders. The common Xq13 chromosome breakpoint and clinical presentation (IASA) among these three patients and the occurrence of an X-linked type of sideroblastic anemia may suggest that an association exists between X chromosome abnormalities and IASA. Perhaps alteration of a gene or chromosome structure in or near band Xq13 predisposes to development of IASA. The fact that two of these patients had preleukemia and the third had overt acute leukemia may imply that patients with IASA and X chromosome abnormalities have a poor prognosis. Cases of IASA without associated X chromosome abnormalities are known; thus, if an association between IASA and an abnormal X chromosome does exist, most likely it involves only some patients with IASA.     

In vitro antagonism of beta-lactam antibiotics by cefoxitin.

We assessed the extent and mechanisms of antagonism of beta-lactam antibiotics by cefoxitin. In tests with 41 gram-negative isolates, cefoxitin antagonized cephalothin, cefamandole, cefsulodin, cefotaxime, moxalactam, ampicillin, carbenicillin, piperacillin, mezlocillin, and azlocillin, but not cephalexin, mecillinam, or N-formimidoyl thienamycin. The extent of antagonism varied with the beta-lactam and genus studied. However, antagonism occurred most often with strains possessing inducible cephalosporinases. Antagonism of cephalothin and cefamandole correlated closely with the induction of beta-lactamases capable of inactivating these drugs. Although antagonism of the remaining drugs occurred more often with strains possessing inducible beta-lactamases, these enzymes did not inactivate the drugs. Morphological studies revealed that cefoxitin inhibited filamentation and lysis produced by various beta-lactam drugs. Results of this investigation suggest that cefoxitin antagonizes beta-lactams via (i) induction of drug-inactivating beta-lactamases, and (ii) the induction of beta-lactamases that cannot inactivate the drug but serve as barriers against access to target proteins. This barrier appears most efficient for drugs that bind to penicillin-binding proteins 1 and 3.     

Comparison of BL-S786 with cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice.

The activity of BL-S786 was compared to that of cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. In broth dilution tests, the activity of BL-S786 was less than cephalothin or cefamandole against Staphylococcus aureus and less than cefamandole or cefoxitin against Haemophilus influenzae. BL-S786 and cefamandole were the two most active drugs against cephalothin-sensitive Enterobacteriaceae. In tests with cephalothin-resistant Enterobacteriaceae, BL-S786 was generally less active than cefamandole but more active than cefoxitin against all strains except Proteus and Providencia. Regardless of the comparative in vitro activity of the four drugs, BL-S786 was the most effective drug in treatment of mice lethally infected with Enterobacteriaceae. Protection from lethality was associated with clearance of bacteremia by each of the four drugs. In several tests where in vitro activity was not predictive of in vivo efficacy, selection of resistance in vivo was found to have occurred.     

Fibrinogen excretion in the urine and immunoreactivity in the kidney serves as a translational biomarker for acute kidney injury

Fibrinogen (Fg) is significantly up-regulated in the kidney after acute kidney injury (AKI). We evaluated the performance of Fg as a biomarker for early detection of AKI. In rats and mice with kidney tubular damage induced by ischemia/reperfusion (I/R) or cisplatin administration, respectively; kidney tissue and urinary Fg increased significantly and correlated with histopathological injury, urinary kidney injury molecule-1 (KIM-1) and N-acetyl glucosaminidase (NAG) corresponding to the progression and regression of injury temporally. In a longitudinal follow-up of 31 patients who underwent surgical repair of abdominal aortic aneurysm, urinary Fg increased earlier than SCr in patients who developed postoperative AKI (AUC-ROC = 0.72). Furthermore, in a cohort of patients with biopsy-proven AKI (n = 53), Fg immunoreactivity in the tubules and interstitium increased remarkably and was able to distinguish patients with AKI from those without AKI (n = 59). These results suggest that immunoreactivity of Fg in the kidney, as well as urinary excretion of Fg, serves as a sensitive and early diagnostic translational biomarker for detection of AKI.