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Biomedical subjects

J M Hammond

Publications and source records attributed to J M Hammond.

At least 73 records · Page 4Linked to original sources
PubMed1993

Neurologic disease requiring long-term ventilation. The role of selective decontamination of the digestive tract in preventing nosocomial infection.

STUDY OBJECTIVE: To evaluate the efficacy of the technique of selective decontamination of the digestive tract (SDD) in preventing secondary infections in patients with neurologic diseases requiring intensive care. DESIGN: Randomized, double-blind, placebo-controlled trial using amphotericin B, polymyxin E, and tobramycin applied to the oropharynx and enterally; all patients received intravenous cefotaxime for 72 h. SETTING: Respiratory ICU. PATIENTS: Forty patients with neurologic diseases requiring ventilation for > 48 h and ICU stay > 5 days. Neurologic diagnosis included acute inflammatory demyelinating neuropathy (15), meningoencephalitis (10), status epilepticus (6), tetanus (6), and myasthenia gravis (3). INTERVENTIONS: Microbiologic surveillance samples of oropharyngeal and tracheal secretions, gastric aspirates, stool, urine, and any other potentially infected sites were taken at the time of ICU admission and twice weekly thereafter until 3 days after discharge from the unit. The SDD was applied every 6 h to the oropharynx and enterally. MEASUREMENTS AND RESULTS: Effective decontamination of the gastrointestinal tract was achieved in the patients receiving the active regimen; however, there was no reduction in the incidence of infections (11 in the active group vs 10 in placebo), and duration of ICU stay (30.1 +/- 22.5 vs 20.6 +/- 17.7 days) and hospital stay (49.3 +/- 31.9 vs 40 +/- 33.4 days) were unaffected as was the mortality (15 percent vs 15 percent). CONCLUSIONS: SDD did not reduce the incidence of secondary infection in patients with neurologic disease, nor did it affect morbidity or mortality; however, it adds considerably to the cost of patient care.

Administration, Oral↗
PubMed1993

Severe pneumococcal pneumonia complicated by massive pulmonary gangrene.

Massive pulmonary gangrene is a rare complication of pneumonia, particularly in the postantibiotic era. We report two cases of community-acquired Streptococcus pneumoniae pneumonia in young patients with a background of heavy alcohol abuse, but no other preexisting disease, which failed to respond to appropriate antibiotic therapy and intensive care. In both, there was extensive unilateral involvement, with initial dense consolidation followed by cavitation, but the previously reported classic later radiologic feature of coalescence into a large cavity with free-floating slough was not seen. Owing to ongoing sepsis with the development of multiple organ failure and the obvious failure of appropriate medical therapy, both patients underwent pneumonectomy with a successful outcome. These cases serve to emphasize the role of surgery in the management of massive pulmonary gangrene.

Acute Disease↗
PubMed1993

The role of insulin-like growth factors and epidermal growth factor-related peptides in intraovarian regulation in the pig ovary.

The autocrine and paracrine role of the insulin-like growth factors (IGFs) and epidermal growth factor (EGF)-related peptides in pig ovary are reviewed. For convenience, each of these regulatory systems is divided into several interactive components: regulated expression of the growth factors, growth factor reception at the cell surface and intracellular action of the growth factors. In addition, the concept of regulated bioavailability and targeting of growth factors in the extracellular space is developed as an important control locus and area for future study. With regard to the IGF system, these components include two ligands--IGF-I and -II, both expressed in the porcine ovary--and the possibility of three receptors. IGF-I and the type I IGF receptor appear to be the most important in stimulating ovarian function and amplifying hormone action. In addition, the 'set-point' of the ovarian IGF system may be determined by the activity of several IGF-binding proteins (IGFBPs). At least four of these proteins are expressed in the pig ovary. Studies of their regulation and action in ovarian cells indicate that they can function as antagonists to FSH and the IGFs. However, preliminary evidence suggests a more dynamic model in which these proteins may direct the site and timing of IGF effects. There are fewer data on the EGF system. At least four EGF-related peptides are expressed in pig ovaries, but insufficient information is available to predict their physiological regulation. These peptides are potent mitogens for ovarian cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Double-blind study of selective decontamination of the digestive tract in intensive care.

Selective decontamination of the digestive tract (SDD), by means of non-absorbable antibiotics, to prevent infection in intensive-care units (ICUs) remains controversial; there is evidence that the regimen reduces the incidence of secondary infection, but no convincing reduction in morbidity or mortality has been shown and the costs and effect on microbial resistance patterns need further study. In a double-blind, placebo-controlled trial, we have tried to find out whether SDD should be used routinely in all ICU patients at high risk of secondary infection. All patients admitted to the ICU who were thought likely to stay in the unit for at least 5 days and to need intubation for longer than 48 h were enrolled and randomly allocated to groups receiving placebo or SDD (amphotericin, colistin, and tobramycin applied to the oropharynx and enterally); all patients received intravenous cefotaxime for 72 h. Of 322 patients randomised, 83 were withdrawn (80 ICU stay or duration of intubation too short, 3 protocol violations). 239 medical, trauma, and surgical patients completed the trial period (114 SDD, 125 placebo). There were no differences between SDD and placebo groups in incidence of infection (30 [26%] vs 43 [34%] patients; p = 0.22), duration of ICU stay (mean 16.2 [14.3] vs 16.8 [12.3] days), hospital stay (29.9 [SD 25.0] vs 31.9 [22.2] days), or mortality (21 [18%] vs 21 [17%]). SDD substantially increased the costs of intensive care. Mechanisms other than bacterial colonisation of the gut may bring about substantial numbers of secondary infections in ICUs. Routine use of SDD in multidisciplinary ICUs cannot be recommended.

Administration, Oral↗
PubMed1992

An African swine fever virus gene with homology to DNA ligases.

Sequence analysis of the SalI g region of the genome of a virulent isolate of ASFV (Malawi Lil 20/1) has revealed an open reading frame with the potential to encode a 48 kilodalton (kD) polypeptide which has significant homology with eukaryotic and prokaryotic DNA ligases. This ASFV encoded gene also contains the putative active site region of DNA ligases including the lysine residue which is necessary for enzyme-adenylate adduct formation, but lacks the C-terminal basic region conserved in other eukaryotic DNA ligases. A novel [32P]-labelled potential DNA ligase-adenylate adduct of M(r) 45 kD was observed upon incubation of ASFV infected cell cytoplasmic extracts with alpha-[32P]-ATP and subsequent analysis of products by SDS/PAGE. These data together suggest that ASFV encodes its own DNA ligase.

Amino Acid Sequence↗
PubMed1992

Gonadotropin and cAMP modulation of IGE binding protein production in ovarian granulosa cells.

Porcine granulosa cells (GC) produce insulin-like growth factor (IGF) binding protein (BP)-3 and IGFBP-2 in culture. A gonadotropin, follicle-stimulating hormone (FSH), dramatically inhibited GC production of these IGFBPs in control cultures and in cultures stimulated by insulin plus epidermal growth factor (EGF) or IGF-I plus EGF. Stimulators of adenylate cyclase (forskolin, cholera toxin) and a derivative of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate, inhibited IGFBP synthesis in a manner similar to FSH. In contrast, the antagonist of cAMP action, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], significantly stimulated production of IGFBP-3 and IGFBP-2 compared with controls. This stimulatory effect of (R)-p-cAMPS was counteracted by cotreatment with FSH in a dose-dependent manner. Finally, treatment of GC cultures with FSH plus 3-isobutyl-1-methylxanthine resulted in a significant reduction in cellular content of mRNA coding for IGFBP-3 with no change in IGFBP-2 mRNA. In summary, agents that elevate intracellular cAMP were found to mimic the effects of FSH on IGFBP production.

Animals↗
PubMed1992

Expression of insulin-like growth factor-binding protein-2 and -3 messenger ribonucleic acid in the porcine ovary: localization and physiological changes.

Insulin-like growth factor-binding protein (IGFBP)-2 and -3 are the most prevalent IGFBPs in porcine follicular fluid, as determined on ligand blots, but little is known about the localization and regulation of their synthesis in vivo. This study was designed to investigate the localization and cyclic regulation of the mRNA for these two IGFBPs in the porcine ovary, RNA was extracted from whole ovaries morphologically classified as immature, preovulatory, and luteal. Northern hybridization analysis of this RNA showed no significant difference in the expression of IGFBP-2 mRNA in these ovaries (OD for preovulatory, luteal, and immature ovaries, 0.076 +/- 0.01, 0.071 +/- 0.01, and 0.10 +/- 0.008/micrograms RNA, respectively). IGFBP-3 mRNA was not different in immature and preovulatory ovaries, but was 10-fold greater (P less than 0.025) in luteal ovaries. Northern analysis of RNA extracted from ovaries also showed no significant change in IGFBP-2 mRNA on days (d) 11, 16, and 21 of the estrous cycle. IGFBP-3 mRNA tended to decrease between d11-16 with the onset of luteal regression and was significantly decreased in d21 preovulatory ovaries to 22% of the values in d11 ovaries. Granulosa, thecal, and luteal cells were also analyzed for IGFBP mRNA. IGFBP-2 mRNA was most abundant in granulosa cells, lower in thecal cells, and lowest in luteal cells. No IGFBP-3 mRNA could be detected in granulosa cells, and luteal cells expressed 15- to 63-fold greater levels than thecal cells. These results show that IGFBP-2 and -3 mRNAs are expressed in specific ovarian cell types and that their expression appears to be independently regulated during the reproductive cycle. This provides further evidence for the importance of these proteins as paracrine/autocrine regulators of ovarian function.

Actins↗
PubMed1992

Insulin and insulin-like growth factors (IGFs) stimulate production of IGF-binding proteins by ovarian granulosa cells.

Ligand blot analysis of granulosa cell (GC)-conditioned culture medium revealed several easily measurable insulin-like growth factor (IGF)-binding proteins (IGFBPs), including IGFBP-3 [40-44 kilodaltons (kDa)] and IGFBP-2 (34 kDa). In the present study, IGF-I, in a dose-dependent manner, significantly stimulated the production of these IGFBPs. Insulin, but not IGF-II, mimicked IGF-I's action on IGFBP-3 and -2 production, but was less potent. The synthetic IGF, long R3-IGF-I, which has very low affinity for IGFBPs and only slightly reduced affinity for the IGF-I (type I) receptor, had significantly greater potency in stimulating IGFBP-3 and -2 production compared to IGF-I. Des-(1-3)-IGF-I had similar effects. IGF-I, IGF-II, and the IGF-I analogs, but not insulin, also induced production of an unidentified 30-kDa IGFBP not normally detectable in these cultures. However, in the presence of epidermal growth factor (which was without independent effect on the 30-kDa IGFBP), insulin also induced this 30-kDa IGFBP. By Northern analysis the expression of IGFBP-3 mRNA was found to be significantly stimulated by IGF-I. In summary, insulin stimulated IGFBP-3 and -2 production in a manner that mimics that of IGF-I and the more potent long R3-IGF-I. However, its low potency suggested that IGFBP production is regulated via the IGF-I (type I) receptor. The much higher potency of long R3-IGF-I compared to that of IGF-I suggests that the IGFBPs themselves modulate the action of IGFs by sequestering exogenous IGFs. Thus, one cellular response to IGF stimulation is the production of IGFBPs, which, in turn, reduce or negate the biological activity of the IGFs. The effects of insulin-like peptides are exerted at least in part by increasing levels of mRNA for specific BPs.

Animals↗
PubMed1992

Etiology and diagnosis of pneumonia requiring ICU admission.

The spectrum of pathogens and the microbiologic investigations used to obtain a diagnosis in 178 patients with severe pneumonia (88 percent requiring intermittent positive-pressure ventilation) are reviewed. Ninety-five patients had primary pneumonia, 31 had nosocomial pneumonia, 24 were immunocompromised patients, and 28 had aspiration pneumonia. While the spectrum of isolates conformed to the usual patterns for the different types of pneumonia, the incidence of Gram-positive infections (15 percent), predominantly Klebsiella pneumoniae, Staphylococcus aureus, (8 percent), and Legionella pneumophila (5 percent) in primary pneumonia was much higher than in community or general hospital-based studies, and only one case of Mycoplasma pneumoniae was identified. Gram stain of sputum or tracheal aspirate taken on intubation in primary pneumonia was reliably predictive of the causative organisms in both Gram-positive and Gram-negative infections when compared with infections proven by blood culture. Serologic studies were valuable in patients in whom no positive microbiologic diagnosis was evident; however, fiberoptic bronchoscopy contributed minimally to the microbiologic diagnosis in this group of patients. The cause of severe primary pneumonia differs from less severe disease, and this should be recognized when selecting empiric antibiotic therapy.

Adolescent↗
PubMed1992

Effect of frequency of administration of exogenous porcine growth hormone on growth and carcass traits and ovarian function of prepubertal gilts.

Three experiments were conducted to examine relationships among dose and frequency of administration of exogenous porcine growth hormone (pGH) on growth traits and ovarian function of prepubertal gilts. In Exp. 1, gilts were treated with 0 or 5 mg of pGH daily for 42 d or 5 mg of pGH daily on alternate weeks over a 42-d period. In Exp. 2, gilts were treated with 0, 2.5, or 5 mg of pGH daily for 31 d or daily on alternate weeks for 31 d. In Exp. 3, gilts received 5 mg of pGH daily on either wk 1, 3, and 5 or wk 2, 4, and 6 during a 42-d period. In all experiments, ADG increased dramatically and feed efficiency improved markedly during treatment with pGH, and both traits declined rapidly during periods when treatment was withdrawn. Gilts treated with pGH daily on alternate weeks tended to be more similar (P greater than .05) to control gilts for growth rate, feed efficiency, and carcass measurements than to gilts that received continuous daily administration of pGH during the entire duration of the experiments. Increased concentrations of estradiol and insulin-like growth factor (IGF)-I in follicular fluid and serum, decreased concentrations of IGF-II in follicular fluid, and increased weights of ovaries were evident as both dose and frequency of exogenous pGH administration increased. Therefore, gilts are extremely sensitive to administration and withdrawal of exogenous pGH during the finishing phase of the production cycle and can respond within 7 d to changes in exogenous pGH treatment regimens. Alternate weekly administration of exogenous pGH in vivo may improve follicular function, as indicated by relationships among IGF-I and IGF-II, estradiol, and progesterone, but fails to improve overall growth and carcass traits compared with controls.

Animals↗
PubMed1991

Vaccinia virus-mediated expression of African swine fever virus genes.

Bacteriophage lambda and plasmid clones containing African swine fever virus (ASFV) DNA inserts, which together covered more than 90% of the genome of a Malawi ASFV isolate (LIL 20/1), were transfected into vaccinia virus (VV)-infected cells. Expression of ASFV-encoded proteins was assayed at late times after VV infection by immunoprecipitation of [35S]methionine-labeled proteins with hyperimmune serum from ASFV-infected pigs, separation of immunoprecipitated proteins by denaturing polyacrylamide gel electrophoresis, and detection by autoradiography. Synthesis of eight additional proteins not observed in control experiments was detected. Seven VV recombinants were constructed, each containing an ASFV DNA insert from a separate bacteriophage lambda clone ranging in size from 9 to 15 kb. BSC40 cells were infected with recombinant viruses and expression of ASFV-encoded proteins assayed at early and late times postinfection. Synthesis of additional proteins, not observed in control experiments, was detected by immunoprecipitation with ASFV antiserum both early and late postinfection with two of these recombinants. In these experiments VV promoters were not included upstream of individual ASFV genes.

African Swine Fever Virus↗
PubMed1991

Identification and regulation of insulin-like growth factor binding proteins produced by hormone-dependent and -independent human breast cancer cell lines.

Using molecular hybridization, ligand blotting and immunoprecipitation, our studies were designed to identify the insulin-like growth factor binding proteins (IGFBPs) produced by human breast cancer cells in culture and evaluate their regulation by estradiol (E2) and polyamines (PA). We demonstrate that the hormone-dependent MCF-7 and -independent BT-20 cell lines express the mRNA for IGFBP-2 (1.7 kb) and secrete this BP (31 kDa) in the conditioned medium. In contrast, the hormone-independent MDA-MB-231 cell line does not express the IGFBP-2 gene, while synthesizing and secreting IGFBP-1. E2 administration (10(-9) M) did not significantly influence IGFBPs secretion in MCF-7 cells. Addition of alpha-difluoromethylornithine (DFMO, 4 mM), an inhibitor of PA biosynthesis, consistently lowered IGFBP-2 mRNA in the MCF-7 and BT-20 cell lines and IGFBP-1 mRNA in MDA-MB-231 cells. Surprisingly, however, this compound either did not influence IGFBPs secretion in MCF-7 cells or actually increased their secretion in the BT-20 and MDA-MB-231 cell lines. PA involvement in IGFBPs production by breast cancer cells is complex and may involve differential regulation of transcriptional and post-translational events.

Breast Neoplasms↗
PubMed1991

The ovarian insulin-like growth factors, a local amplification mechanism for steroidogenesis and hormone action.

The importance of the ovarian insulin-like growth factors (IGFs) has been suggested by data from numerous laboratories and several approaches in the last several years. In the aggregate, these data indicate that this system could function as an important local amplification mechanism for steroidogenesis and gonadotropin action. Studies supporting this hypothesis have described several interacting components of this autocrine/paracrine system. First, the several types of ovarian cells possess an IGF-response system, which includes receptors for IGFs and an effective intracellular transduction system. The IGFs can promote growth and/or differentiation of ovarian cells, and their predominant actions depend on the nature of the cells and the presence of additional modulating factors. The biochemical events leading to enhanced steroidogenesis are now understood in considerable detail and include induction of several steps in the cAMP-dependent steroidogenic cascade. The second component of the ovarian IGF system comprises hormone-responsive local production of IGFs. Both IGF-I and IGF-II may be secreted; gonadotropins, gonadal steroids and locally produced growth factors can regulate the IGF system at this level. Finally, ovarian cells secrete a heterogeneous and complex family of IGF-binding proteins (IGFBPs). These proteins can impact on multiple ovarian functions in a manner which is generally opposite to that of the IGFs themselves. As is the case for the IGFs, the secretion of these proteins by ovarian cells is regulated by gonadotropins and locally produced ovarian factors. Collectively, these several components provide an integrated, synergistically cooperative local network to promote gonadotropin-dependent growth and differentiation in the ovary.

Female↗
PubMed1991

Intensive care management of community-acquired Klebsiella pneumoniae.

The clinical features of 18 patients with Klebsiella pneumoniae requiring intensive care unit (ICU) management are presented. All patients required ventilatory support; 17 were given constant positive pressure ventilation and 10 required greater than 10 cm positive end expiratory pressure. The clinical picture was characteristic: pre-existing medical disease, clinical features of severe pneumonia and copious purulent bronchial secretions, Gram--ve organisms on Gram's stain and lobar consolidation on the chest radiograph were common. Septicaemic shock, confusion and uncompensated metabolic acidosis were the presenting clinical features predicting a poor outcome. Antimicrobial chemotherapy, that combined an aminoglycoside and a third generation cephalosporin to ensure adequate early antibiotic serum levels, may help to improve the prognosis.

Acidosis↗
PubMed1991

Characterization of insulin-like growth factor-binding proteins of porcine ovarian follicular fluid.

Using competitive ligand-binding studies, ligand blotting, and immunoprecipitation, we have characterized the insulin-like growth factor (IGF)-binding proteins (BPs) of porcine follicular fluid. Competitive ligand-binding studies revealed a preference of ovarian IGFBPs for IGF-II over IGF-I. Follicular fluid from small, 1-3-mm follicles had nearly twice the binding capacity for IGFs as that from large, 6-10-mm follicles. Ligand blots of porcine follicular fluid resolved 5 major bands of IGF-binding activity having apparent molecular sizes of 44, 40, 34, 29, and 22 kDa. The 40-44-kDa bands were immunoprecipitated by an antibody to porcine IGFBP-3, the acid-stable subunit of the 150-kDa growth hormone-dependent IGF-binding protein complex of porcine serum. The 34-kDa band was immunoprecipitated by an antibody to rat IGFBP-2, the major IGF-binding protein found in fetal rat serum. To date we have been unable to immunoprecipitate the 29- and 22-kDa bands with any of the antibodies tested, including a panel of monoclonal antibodies to human IGFBP-1, the amniotic fluid IGF-binding protein. The 40-44-kDa species (IGFBP-3) was the predominant form and was equally abundant in fluid from large and small follicles. In contrast, the smaller forms, including IGFBP-2 and the 29- and 22-kDa forms were significantly more prominent in fluid from small follicles. In view of other studies indicating a significant effect of IGFBPs on ovarian cell function, follicular IGFBPs may play an important role in the IGF autocrine/paracrine regulatory system of the ovary.

Animals↗
PubMed1991

Effect of constant versus adjusted dose of exogenous porcine growth hormone (pGH) on growth and reproductive characteristics of gilts.

Growth, carcass traits, and selected reproductive characteristics were evaluated in prepubertal gilts treated with either a constant mass of pGH or a mass of pGH adjusted periodically for changes in BW. Gilts (64 kg, n = 24) were given 24 daily injections of either vehicle (C; control) or one of two doses of pGH: 70 micrograms/kg of BW, with dose adjusted every 5th d for changes in BW (A; adjusted), or 70 micrograms/kg of initial BW (U; unadjusted). Gilts were slaughtered on d 25. Gilts treated with pGH had higher ADG (P less than .002) and improved feed efficiency (kg of feed/kg of gain; P = .0003) compared with controls. Weights of adrenal glands, liver, heart, and kidney were higher (all P less than .01) for Groups A and U than for Group C gilts. Average backfat thickness was less (P less than .004) for A and U gilts than for C gilts and less for Group A than for Group U (P less than .02). Furthermore, growth and carcass traits were similar (P greater than .05) for Groups A and U, except for measurements of first rib backfat, last rib backfat, and average backfat depth (P less than .05). Culture of granulosa cells (GC) was employed to assess ovarian function. Addition of FSH to the culture media enhanced secretion of progesterone (P4) by cultured GC from all in vivo treatments compared with unsupplemented cultures of GC (P less than .05). Addition of LH to the culture media enhanced secretion of P4 by cultured GC from pGH-treated gilts only (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗