The pivotal role of adrenomedullin in producing hyperdynamic circulation during the early stage of sepsis

BACKGROUND: Initial cardiovascular responses during sepsis are characterized by hyperdynamic circulation. Although studies have shown that a novel potent vasodilatory peptide, adrenomedullin (ADM), is up-regulated under such conditions, it remains unknown whether ADM is responsible for initiating the hyperdynamic response. OBJECTIVE: To determine whether increased ADM release during early sepsis plays any major role in producing hyperdynamic circulation. DESIGN, INTERVENTION, AND MAIN OUTCOME MEASURE: Synthetic rat ADM (8.5 microg/kg of body weight) was infused intravenously in normal rats for 15 minutes at a constant rate. Cardiac output, stroke volume, and microvascular blood flow in various organs were determined immediately as well as 30 minutes after ADM infusion. At 30 minutes after infusion, plasma ADM level was also measured. In additional groups, rats were subjected to sepsis by cecal ligation and puncture. At 1.5 hours after cecal ligation and puncture, specific anti-rat ADM antibodies were infused, which completely neutralized the circulating ADM. Various hemodynamic variables were measured 5 hours after cecal ligation and puncture (ie, the early stage of sepsis). RESULTS: Cardiac output, stroke volume, and microvascular blood flow in the liver, small intestine, kidney, and spleen increased, and total peripheral resistance decreased 0 and 30 minutes after ADM infusion. In addition, plasma levels of ADM increased from the preinfusion level of 92.7+/-5.3 to 691.1+/-28.2 pg/mL 30 minutes after ADM infusion, which was similar to ADM levels observed during early sepsis. Moreover, 5 hours after the onset of sepsis, cardiac output, stroke volume, and microvascular blood flow in various organs increased and total peripheral resistance decreased. Administration of anti-ADM antibodies, however, prevented the occurrence of the hyperdynamic response. CONCLUSIONS: The results suggest that increased ADM production and/or release plays a major role in producing hyperdynamic responses during early sepsis. Since our previous studies have shown that vascular responsiveness to ADM decreases in late sepsis, maintenance of ADM vascular responsiveness by pharmacological agents during the course of sepsis may prevent transition from the hyperdynamic to the hypodynamic state.     

Epidural anaesthesia for caesarean section in an achondroplastic dwarf

Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. Telomerase activation has been seen in many immortal cell lines and cancers. Telomerase activity was analyzed in prostate carcinoma; in coexistent prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), atrophy and normal tissue; and in benign prostate glands. Telomerase activity was detected in 80 of 87 (92%) prostate cancers. Forty-one matched samples (from a total of 32 cases) were available for comparative analysis. The presence of telomerase activity in adjacent PIN, BPH, and normal tissue was correlated with telomerase activity in the malignant epithelium. In these adjacent tissues, telomerase activity was found in 11 of 15 (73%) PINs, 13 of 26 (50%) BPHs, and 1 of 6 (16%) atrophy and 4 of 11 (36%) normal tissues. In contrast to the BPH tissue from cancer-bearing glands, all 16 BPH specimens from patients only diagnosed with BPH were telomerase activity negative. In cancer samples, there was no correlation between telomerase activity and Gleason grade or preoperation prostate-specific antigen level. Our data indicate that telomerase activity is present in most prostate cancers. The high rate of telomerase activity in the benign-appearing areas of these glands may be attributed either to the presence of occult cancer cells or to early molecular alterations of cancer that were histologically inapparent.     

Nucleolar organizer regions in lymphomas: a quantitative study

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NORs) have been studied in paraffin sections of 76 non-Hodgkin's lymphomas, five normal lymph nodes, and five lymph nodes. The mean number of nucleolar organizer regions per nucleus was 1.19 (SD:0.09) for normal lymphocytes, 3.04 (SD:0.14) for reactive lymph nodes, 2.79 (SD:0.44) for low-grade lymphomas, 6.33 (SD:1.58) for intermediate-grade lymphomas, and 10.53 (SD:1.97) for high-grade lymphomas. There were highly significant differences in Ag-NOR counts among the groups (p < 0.001). The Ag-NOR regions were often observed in nuclei in areas where nucleoli themselves were invisible. It is suggested that this method is useful in diagnostic histopathology and in differentiation of the grade of lymphomas.     

Preparation of polyaniline montmorillonite clay composites for the removal of diethyl hexyl phthalate from aqueous solutions

The work presents the synthesis of polyaniline functionalized montmorillonite (PANI/MMT) clay composites and evaluation of their performance as an adsorbent for the mitigation of toxic diethyl hexyl phthalate (DEHP) from water. The formation of composite was confirmed by different analytical techniques such as FTIR, zeta potential analysis, XRD, SEM, and AFM. The adsorption capacity of PANI/MMT was superior to MMT. DEHP followed partition mechanism on PANI/MMT whereas MMT favored surface adsorption mechanism. The performance of PANI/MMT for DEHP removal was unaffected by the change in pH of solution, change in salinity, and hardness contents in aqueous system and consecutive adsorption desorption cycles compared to MMT. Furthermore, both PANI/MMT and MMT exhibited greater adsorption capacities as compared to the previously published work and showed satisfactory performance in real water samples.     

An adenovirus type 5 mutant with the preterminal protein gene deleted efficiently provides helper functions for the production of recombinant adeno-associated virus

Production of recombinant adeno-associated virus (rAAV) requires helper functions that have routinely been provided by infection of the producer cells with adenovirus. Complete removal and/or inactivation of progeny adenovirus, present in such rAAV preparations, presents significant difficulty. Here, we report that an adenovirus type 5 (Ad5) mutant with the preterminal protein (pTP) gene deleted can provide helper function for the growth of rAAV. At high multiplicity, Ad5dl308DeltapTP was as efficient as the phenotypically wild-type Ad5dl309 in permitting growth of rAAV. Use of Ad5dl308DeltapTP, which is incapable of replication in the absence of complementation for pTP, as a helper avoids the need to remove contaminating adenovirus infectious activity by heat inactivation or by purification. Comparison of the transducing ability of rAAV generated with either Ad5dl308DeltapTP or Ad5dl309 as a helper demonstrated that the heat inactivation protocol generally used does not remove all of the helper Ad5dl309 function.     

Massive gastric enlargement with delayed presentation of congenital diaphragmatic hernia: report of three cases and review of the literature

In three cases of congenital diaphragmatic hernia presenting long after the newborn period, there was striking enlargement of the intraabdominal stomach. In each case there was herniation of the entire small bowel into the thorax and absence of a hernial sac. Despite the enormous capacity of the stomach, which was suggestive of obstruction preoperatively, no site of obstruction could be demonstrated at operation. This enlargement disappeared following surgical repair of the hernia.     

Pesticides and the South African population

Legislation which has a bearing on pesticides, and its current implementation by the State departments of Agricultural Technical Services and Health, are discussed. Organophosphate compounds account for about 80% of all deaths from pesticides and for about 60% of non-fatal cases of intoxication. In South Africa, levels of lipophilic organochlorine compounds in human adipose tissue are generally well under the world average and are demonstrating a progressive downward trend.