Multilocular renal cyst. A hamartoma with potential for neoplastic transformation?

Multilocular renal cyst is a pathologically distinctive lesion of uncertain pathogenesis that usually presents as a large abdominal mass in male infants or middle-aged women. We performed detailed light and electron microscopic studies of three nephrectomy specimens that contained multilocular cysts and attempted to correlate their morphology with various theories of pathogenesis. In one of our cases, a microscopic focus of clear cells that resembled renal cell adenocarcinoma was observed in the wall of one locule. Although such a finding has been reported previously, the lack of well-documented cases with metastases suggests that the prognosis for patients with this lesion remains uniformly excellent.     

Reflex inhibition of the quadriceps after meniscectomy: lack of association with pain

We have examined the severity and duration of reflex inhibition of quadriceps activation after arthrotomy and meniscectomy, its relationship with pain, and the effect of local anaesthesia on this relationship. Fourteen men, on completion of medial meniscectomy by arthrotomy, received either 10 ml (B10 group) or 15 ml (B15 group) of 0.5% bupivacaine hydrochloride ('Marcaine Plain') into the knee, or no injection (control group). Reflex inhibition of quadriceps was measured as the percentage reduction, from the ipsilateral preoperative value, in the integrated surface electromyogram recorded during maximal voluntary isometric contractions with the knee in extension. Pain during each contraction was recorded on a linear analogue scale. Unoperated limbs showed no evidence of quadriceps inhibition. In the operated limbs, at 1-2 h post-operatively, controls had both severe inhibition (median = 62%) and severe pain on attempting a maximal quadriceps contraction. The B10 group had similar inhibition but less pain (P less than or equal to 0.005, Wilcoxon 2-sample, 1-tailed test). In the B15 group both inhibition (P less than or equal to 0.05) and pain (P less than or equal to 0.01) were less than in the controls. These effects of bupivacaine had been lost by 4-5 h post-operatively. At 3-4 days, inhibition was still severe (median = 75%) in all three groups of patients but pain was only mild or absent. At 10-15 days, median inhibition was still 35%, but there was little or no pain. We conclude that postmeniscectomy inhibition is not simply due to perceived pain but is due, at least in part, to stimuli from the knee.     

Low-grade squamous intraepithelial lesions: Cytologic predictors of biopsy Confirmation

One hundred and seven smears demonstrating a low-grade squamous intraepithelial lesion (LSIL) were analyzed for features predicting subsequent biopsy confirmation. Twelve (29%) of 41 smears showing few LSIL cells were biopsy confirmed compared to 33 (60%) of 55 containing an intermediate number of LSIL cells and 9 (82%) of 11 displaying many LSIL cells (P < 0.002). Thirty-seven (47%) of 78 smears showing mainly condylomatous atypia (CA), 7 (54%) of 13 revealing predominantly cervical intraepithelial neoplasia 1 (CIN 1), and 10 (63%) of 16 displaying both CA and CIN 1 were histologically confirmed (N.S.). Biopsy confirmation was obtained in 35 (65%) of 54 women whose repeat smears obtained at colposcopy demonstrated SIL compared to four (15%) of 26 patients whose repeat smears were normal or contained atypical squamous cells of undetermined significance (P < 0.001). These results suggest that the number of diagnostic cells in an LSIL smear predicts biopsy confirmation and affirm the validity of combining CA and CIN 1 under the category of LSIL in the Bethesda System. © 1994 Wiley-Liss, Inc.     

Effects of dichloromethylene diphosphonate on skeletal mobilization of calcium in multiple myeloma

Dichloromethylene diphosphonate (Cl2MDP), an inhibitor of oestoclast activity, was evaluated for its ability to decrease the excessive mobilization of skeletal calcium that complicates multiple myeloma. Ten patients with active myeloma, wide-spread bone disease, and hypercalciuria were studied in a double-blind, placebo-controlled, crossover-designed trial in which they took Cl2MDP for eight weeks and placebos for eight weeks. Two patients died during the placebo phase; of eight patients who received Cl2MDP, seven had rapid, sustained, and highly significant (P less than 0.001) decreases in urinary excretion of calcium. Six also had significant decreases in hydroxyproline excretion, and five reported lessening of skeletal pain. On patient did not respond. Although the patients received concurrent chemotherapy during the study, concentrations of myeloma proteins actually increased or decreased only slightly, indicating the declines in hypercalciuria resulted from Cl2MDP and not from improvement in the underlying disease. We conclude that Cl2MDP is a potentially useful inhibitor of osteoclast-mediated bone erosion in multiple myeloma.     

Epinephrine improves expiratory flow rates in patients with asthma who do not respond to inhaled metaproterenol sulfate

One hundred patients with acute asthma and peak expiratory flow rates (PEFR) less than 150 L/min were randomized and treated in a double-blind treatment protocol with either metaproterenol sulfate aerosol (MPA) inhalation and placebo injection or epinephrine injection (EPI) and inhaled placebo at entry and at 30 and 60 minutes, and then were treated with the crossover comparison regimen at 120, 150, and 180 minutes. The two groups had similar entry PEFRs and FEV1 (MPA, 112 L/min; 0.94 L, respectively; EPI, 111 L/min; 0.85 L, respectively) and similar plasma theophylline levels (MPA, 12.2 micrograms/ml; EPI, 13.8 micrograms/ml). PEFR and FEV1 were measured every 30 minutes for 4 hours. Mean expiratory flow rates among both groups were similar at entry and at 120 and 240 minutes. At 120 minutes, flow rates had improved in 28/46 MPA-treated patients (61%) and 48/54 EPI-treated patients (89%). Among these improved patients, flow rates were significantly higher in the MPA-treated group. At 120 minutes, 18/46 MPA-treated patients (39%) and 6/54 EPI-treated patients (11%) had PEFRs less than 120 L/min and PEFR and FEV1 less than 120% of baseline values (p less than 0.01). In 13 of these 18 MPA-treated patients who did not improve compared to 1/6 EPI-treated patients who did not improve, PEFRs were greater than 120 L/min, and PEFR and FEV1 had increased 20% or more above baseline values after treatment with the crossover comparison regimen (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Aetiology of congenital absence of vas deferens: genetic study of three generations

Bilateral congenital absence of the vas deferens (CAVD) is aform of male sterility (found in otherwise normal men) of unknownaetiology. Because males with cystic fibrosis (CF) almost invariablyhave CAVD as well, we investigated the hypothesis that men withisolated CAVD might share a common genetic background with maleswith CF. Genetic testing for CF was carried out in three generationsof subjects: 44 patients with CAVD and their wives, 24 of theirparents, and 13 of their offspring generated by microsurgicalepididymal sperm aspiration (MESA) and in-vitro fertilization(IVF). DNA extracted from peripheral lymphocytes was amplifiedby the polymerase chain reaction (PCR) and then analysed for12 mutations in the cystic fibrosis transmembrane conductanceregulatory (CFTR) gene. Among 44 patients tested with CAVD,26 (59%) were positive for at least one CF mutation, while thecarrier frequency for CF mutations in the general populationis only 4%. Four patients were found to be compound heterozygotes,three with genotypes Delta F-508/R117H, one with R553X/R117H.Among 24 parents tested, 15 (seven fathers, eight mothers) hadsons with CAVD who were positive for CF mutations. Of these,nine (four fathers and five mothers) were found to be carriersfor CF mutations. These four fathers, although carriers of CFmutations, were obviously fertile. Of the 13 offspring tested,six (three boys and three girls) had CF positive fathers. Ofthese, three (two girls and one boy) were found to be carriersfor CF mutations. These MESA/IVF children are the first offpsringto whom men with CAVD have been able to transmit CF mutations.All of the MESA/IVF male offspring (like their grandfathers)had a normal vas deferens bilaterally, including one carrierfor Delta F-508. This study revealed, by genetic testing ofotherwise normal men with sterility caused by CAVD, a new populationof patients with a variant form of CF and highlighted the possibilitythat carrier frequency for CF is higher than previously thought.Compound heterozygosity for CF mutations and not carrier conditionis associated with isolated CAVD. It is concluded that geneticcounselling and screening for CF should be offered to couplesundergoing sperm aspiration and IVF procedures when CAVD isa factor in their infertility.     

Effects of inhaled beclomethasone dipropionate and alternate-day prednisone on pituitary-adrenal function in children with chronic asthma.

Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corticosteroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 microgram per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together.     

Chemical modifications of band 3 protein affect the adhesion of Plasmodium falciparum-infected erythrocytes to CD36

The role of the erythrocyte anion exchanger, band 3 protein (AE1), in the adhesion of Plasmodium falciparum-infected erythrocytes to CD36 and thrombospondin (TSP) was studied. Two specific anion exchange inhibitors that bind covalently to different regions of the band 3 molecule affected cytoadherence in dissimilar ways. Modification of lysine 539 by diisothiocyanostilbene sulfonic acid (DIDS) resulted in a significant reduction in the adhesive properties of parasitized erythrocytes for CD36, but not TSP, whereas treatment with fluorescein-5-maleimide, which modifies lysine 430, was without effect on both TSP and CD36 binding. The adhesive properties of the DIDS binding region (DBR) was demonstrated by competition experiments using synthetic peptides and by direct interaction of such peptides with CD36 transfected CHO cells. The results suggest that host membrane proteins such as AE1 contribute to the adhesion of malaria-infected erythrocytes to CD36.     

Hungry, but not thirsty, rats prefer flavors paired with ethanol

The present experiments examined the reinforcing effects of an ethanol (EtOH) unconditioned stimulus (UCS) on conditioned flavor preferences in food-deprived rats and in water-deprived rats. In Experiment 1A food and water deprived animals received distinct conditioning treatments. One half of the animals were intragastrically intubated with EtOH (0.5 g/kg), and thereafter allowed 20 min free access to similar flavored drinking solutions. Remaining animals were intubated with distilled water. All animals received 15 presentations of an EtOH-paired flavor. A two-bottle preference test was subsequently used to evaluate preferences or aversions to flavors paired with EtOH in food-deprived and water-deprived animals. Results of Experiment 1A showed that food-deprived animals preferred the flavor associated with EtOH. Conversely, preferences for EtOH-paired flavors were not established in water-deprived animals. In Experiment 1B deprivational states of animals used in Experiment 1A were reversed without further drug training. Following a two week habituation period to deprivation state animals again received a two-bottle preference test to re-evaluate preferences or aversions to the EtOH-paired flavors. Results of those manipulations indicated that an ethanol aversion was established in the water-deprived animals. Those results indicated that water-deprived animals of Experiment 1B reversed their EtOH-paired flavor preference when the caloric need associated with food deprivation conditions was eliminated. Since deprivational state determined the development of EtOH preferences, the present results indicate that caloric need may play an initial role in establishing conditioned preferences for EtOH.     

Adherence of Vero cytotoxin-producing Escherichia coli of serotype O157:H7 to human epithelial cells in tissue culture: role of outer membranes as bacterial adhesins

Escherichia coli of serotype O157:H7 are Vero cytotoxin-producing enteric pathogens that have recently been associated with outbreaks of haemorrhagic colitis, sporadic cases of haemorrhagic colitis and with the haemolytic uraemic syndrome. The organisms demonstrate attaching and effacing binding to the caecum and colon of orally infected gnotobiotic piglets, chickens and infant rabbits. E. coli O157:H7 cells adhere to the surface but do not invade the cytoplasm of human epithelial cell lines in tissue culture. Since outer membranes, lipopolysaccharides and flagella have been identified as bacterial adhesins on other enteric pathogens, we evaluated their roles in the binding of non-fimbriated E. coli O157:H7 to HEp-2 cells. Hyperimmune rabbit antisera were prepared to whole cells, outer membranes and flagella of E. coli O157:H7. The presence of antibody to homologous antigen was confirmed by dot blot immunoassays. Both antisera and purified outer membrane and flagellar antigens were co-incubated with bacteria and HEp-2 cells to quantitate inhibition of bacterial attachment. Adherence of E. coli O157:H7 to tissue culture cells was inhibited by rabbit antisera raised to whole cells (76.0 +/- 5.6% inhibition compared with bacterial adherence in the presence of pre-immune rabbit serum) and outer membranes (69.2 +/- 3.4% inhibition). In contrast, inhibition of bacterial attachment to tissue-culture cells was significantly less when two antisera to H7 flagella were co-incubated with E. coli O157:H7 and HEp-2 cells (12.4 +/- 7.6%; 6.0 +/- 3.5% inhibition). Outer-membrane extracts inhibited adherence to E. coli O157:H7 to HEp-2 cells in a concentration dependent manner whereas isolated flagella and lipopolysaccharide antigens did not inhibit bacterial attachment.(ABSTRACT TRUNCATED AT 250 WORDS)