The relationship between blood lactate and survival following the use of adrenaline in the treatment of septic shock.

This prospective observational study evaluates the relationship between adrenaline, lactate and intensive care unit survival in septic shock. Forty patients requiring adrenaline therapy for a first episode of septic shock acquired > 24 hours after admission to the intensive care unit had blood lactate levels measured two-hourly over a 24-hour period. Adrenaline therapy was escalated until target mean arterial pressure was reached. The lactate index was calculated as the ratio of maximum lactate increase to the adrenaline increase. Lactate increased from 2.3 to 2.9 mmol x l(-1) (P = 0.024) and the mean adrenaline increase was 0.14 microg x kg'.minute(-1). Peak lactate correlated with peak adrenaline (rho = 0.34, P = 0.032). Lactate index was the only independent predictor of survival after controlling for age and Acute Physiological and Chronic Health Evaluation II score (odds ratio 1.14, 95% confidence interval 1.03 to 1.26, P = 0.009). A high lactate following adrenaline administration may be a beneficial and appropriate response.

Is 0.6T magnetic resonance mammography adequate in the detection of breast cancer?

PURPOSE: To evaluate whether relevant diagnostic information can be achieved when using magnetic resonance mammography (MRM) on mid-field as a supplement to conventional imaging and clinical examination in women with primary breast cancer. MATERIAL AND METHODS: 30 women (55 breasts containing 49 malignant tumors) planned for uni- or bilateral mastectomy were examined with dynamic MRM on mid-field, 0.6T. The women were examined with mammography (M) and ultrasonography (US) prior to MRM. The descriptions of the conventional examinations were evaluated retrospectively, whereas the MRM was evaluated prospectively, with knowledge of the M+US findings. Imaging findings suggesting malignancy were registered and correlated with pathology after mastectomy. A home-made rating system for evaluation of the detected lesions was tested. RESULTS: MRM detected seven additional malignant tumors, failed to detect three lesions and characterized four as gray-zone lesions according to the rating system. Sensitivity of finding the tumors with M+US was 79.0%, with a PPV for malignant tumors of 84.4%. One breast in which MRM found a malignant tumor had not initially been examined with US. Sensitivity with MRM was 91.6%, with a positive predictive value of malignant tumors of 97.7%. CONCLUSION: MRM on mid-field seems to improve the detection of cancers when used as a supplement to M+US in women with primary breast cancer. We believe that the results are fair compared to MRM on high-field, although further research and refinement are needed.

A systematic review of stapled hemorrhoidectomy.

HYPOTHESIS: Use of circular stapled hemorrhoidectomy will result in the same or improved safety and efficacy outcomes as those of the conventional methods for hemorrhoidectomy in patients with hemorrhoids. DATA SOURCES: Studies on stapled hemorrhoidectomy were identified using PREMEDLINE and MEDLINE (June 1966-June 2001), EMBASE (January 1980-June 2001), Current Contents (June 1993-June 2001), Ovid HEALTHSTAR (January 1975-June 2001), the National Institutes of Health Clinical Trials database (searched June 13, 2001), and The National Coordinating Centre for Health Technology Assessment database (searched June 14, 2001). The search terms were as follows: haemorrhoid* and (stapl* or convent*) or hemorrhoid* and (stapl* or convent*). The Cochrane Library (2001, issue 2) was searched using the search terms haemorrhoid* or hemorrhoid*. STUDY SELECTION: Articles detailing randomized controlled trials were included if they compared circular stapled with conventional hemorrhoidectomy and provided relevant safety and efficacy outcome information. DATA EXTRACTION: Data from all included studies were extracted using standardized data extraction tables that were developed a priori. In addition, the randomized controlled trials were examined with respect to the adequacy of allocation concealment, handling of those unavailable for follow-up, and any other aspect of the study design or execution that may have introduced bias. DATA SYNTHESIS: Seven randomized controlled trials met the inclusion criteria. A meta-analysis was conducted when the studies had comparable outcomes, inclusion criteria, and follow-up. There was reasonably clear evidence in favor of the stapled procedure for bleeding at 2 weeks (relative risk, 0.55; 95% confidence interval, 0.37-0.82) and length of hospital stay (weighted mean difference, -0.89 days; 95% confidence interval, -1.42 to -0.36). Other less robust results in favor of the stapled hemorrhoidectomy related to pain, bleeding, anal discharge, wound healing, tenderness to per rectal examination, incontinence scores, earlier return of bowel function, analgesic requirement, and resumption of normal activities. One trial showed that prolapse occurred at significantly higher rates in the stapled hemorrhoidectomy group. However, the outcomes were poorly reported and generally showed statistically significant heterogeneity. CONCLUSIONS: Stapled hemorrhoidectomy may be at least as safe as conventional hemorrhoidal surgical techniques. However, the efficacy of the stapled procedure compared with the conventional techniques could not be determined. More rigorous studies with longer follow-up periods and larger sample sizes need to be conducted.

Environmental, medical, and family history risk factors for Parkinson's disease: a New England-based case control study.

Controversy persists about the etiology of Parkinson's disease (PD). Pesticides, herbicides, well-water consumption, head injury, and a family history of PD have been reported as risk factors for PD. The purpose of this study was to (1) investigate the impact of environmental factors on PD risk (2) estimate the chronology, frequency, and duration of those exposures associated with PD; and (3) investigate the effects of family history on PD risk. One-hundred and forty PD cases were recruited from Boston University Medical Center. The control group was composed of 147 friends and in-laws of PD patients. Environmental, medical, and family history data were obtained by structured interview from each participant for events recalled prior to PD onset for cases, or corresponding censoring age for controls (mean age = 56 years of age for each group). A traditional stratified analysis, adjusting for birth cohort and sex, was employed. Four factors were associated with increased risk for PD: (1) head injury (OR=6.23, confidence interval [CI]: 2.58-15.07); (2) family history of PD (OR=6.08, CI: 2.35-15. 58); (3) family history of tremor (OR=3.97, CI: 1.17-13.50); and (4) history of depression (OR=3.01, CI: 1.32-6.88). A mean latency of 36. 5 (SE=2.81) years passed between the age of first reported head injury and PD onset. A mean latency of 22 (SE=2.66) years passed between the onset of the first reported symptoms of depression and onset of PD. Years of education, smoking, and well-water intake were inversely associated with PD risk. PD was not associated with exposure to pesticides or herbicides. These findings support the role of both environmental and genetic factors in the etiology in PD. The results are consistent with a multifactorial model. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:742-749, 1999.

H2 histaminergic control of inhibition of eating induced by intragastric NaCl in rats.

A role for endogenous histamine and histamine receptor subtypes in mediating the inhibition of eating induced by intragastric (i.g.) hypertonic NaCl was examined in adult male Sprague-Dawley rats surgically equipped with a chronic gastric catheter. The i.g. infusion of 2 mL 900 or 1,800 mOsm/kg of NaCl inhibited: 1) ingestion of pellets in rats eating after 24-h food deprivation; and 2) ingestion of cookies in rats eating without prior deprivation. The H1 receptor antagonists dexbrompheniramine (DXB; 1 mg/kg) and pyrilamine (PYR; 4 mg/kg) did not attenuate the inhibitory effects of i.g. 900 or 1,800 mOsm/kg of NaCl for rats eating pellets and for rats eating cookies. The H2 antagonists cimetidine (CIM; 16 mg/kg) and metiamide (MET; 16 mg/kg) attenuated the inhibitory effects of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cookies, but intracerebroventricular (i.c.v.) infusion (through a chronic indwelling cannula) of 100 microg of CIM did not mimic this effect of intraperitoneal (i.p.) CIM. The i.p. CIM failed to attenuate the inhibition of eating cookies produced by i.p. octapeptide of cholecystokinin (CCK-8; 3 microg/kg). The H3 antagonist thioperamide (TH; 10 mg/kg i.p.) and the H3 agonist R-alpha-methylhistamine (RAM; 3 mg/kg i.p.) did not alter the inhibitory effect of i.g. 1,800 mOsm/kg of NaCl for rats eating cookies. Combined treatments of systemic DXB plus CIM, and DXB plus CIM plus thioperamide (TH) did not reverse the inhibitory effects of i.g. 1,800 mOsm/kg of NaCl upon ingestion of cookies. Finally, i.p. DXB, but not CIM, attenuated the ability of i.g. 900 mOsm/kg of NaCl to increase water intake; conversely, i.p. CIM, but not DXB, attenuated the ability of i.g. 900 mOsm/kg of NaCl to inhibit eating of cookies. These findings demonstrate a double dissociation of effects upon ingestive behavior: H1, but not H2, antagonism attenuates the effect of i.g. hypertonic NaCl on water intake, whereas H2, but not H1, antagonism attenuates the inhibition of eating produced by i.g. hypertonic NaCl. These results demonstrate that different subtypes of peripheral and/or central histamine receptors contribute to different behavioral consequences of postprandial gastrointestinal osmotic loads in rats.

Histochemical detection of lymphatic drainage pathways in the middle nasal meatus.

Following extensive middle meatal antrostomy, even without manipulation inside the maxillary sinus, a reactive edema of the maxillary sinus mucosa may be subsequently detected. A presumptive correlation has been established between this particular mucosal reaction and insufficient maxillary lymphatic drainage. Histochemical examination of the lymphatic drainage pathways was carried out on surgical specimens. During the performance of surgical maxillary fenestrations, 80 surgical specimens of the middle nasal meatus were obtained including adjacent parts of the medial maxillary wall. The specimens were subjected to visualization of lymphatic vessels based on the histochemical detection of 5'-nucleotidase according to Werner (1993). Both the nasal and the maxillary sinus mucosa showed a distinct superficial and deep longitudinal lymphatic capillary network (15-200 mu phi) with an orientation towards the natural maxillary sinus ostium. The density of the network increased from cranial to caudal, from dorsal to ventral and reached maximum density at the natural maxillary ostium. Lymphatic vessels of the maxillary sinus mucosa were thin but numerous in comparison to nasal vessels. The maxillary lymphatic capillary network showed direct connections to the nasal vessels, not only along the mucosal folds of the primary maxillary sinus ostium, but also in most cases (57%) transmurally through the natural bony gaps of the uncinate process. Grünwald's theory (1910) which states that lymphatic drainage of the maxillary sinus is established exclusively along the mucosal pane through the natural ostium was disproved. Maxillary mucosal congestion subsequent to extensive middle meatal antrostomy may be explained by ablation of the intramural and transmural lymphatic drainage pathways.

A basic isozyme of yeast glyceraldehyde-3-phosphate dehydrogenase with nucleic acid helix-destabilizing activity.

A nucleic acid helix-destabilizing protein has been purified from Saccharomyces cerevisiae using affinity chromatographic techniques. Crude protein extracts at low ionic strength (approx. 0.05 M) were applied sequentially to tandem columns of native DNA-cellulose, aminophenyl-phosphoryl-UMP-agarose, poly(I . C)-agarose, poly(U)-cellulose and denatured DNA-cellulose. The 2 M NaCl eluant of the poly(U)-cellulose column was dialyzed to low ionic strength and recycled through native DNA-cellulose, poly(I . C)-agarose and poly(U)-cellulose. Purified helix-destabilizing protein eluted from the poly(U)-cellulose between 0.1 and 0.5 M NaCl. On the basis of enzymatic activity, immunological cross-reactivity, mobility on SDS gels, amino acid analysis and preliminary peptide mapping experiments, this material was identified as an isozymic fraction of glyceraldehyde-3-phosphate dehydrogenase. The major crystallizable isozyme of this enzyme from yeast is, however, considerably more acidic than the helix-destabilizing protein, and displays significantly lower helix-destabilizing activity. Stoichiometric levels of the isolated protein at low (approx. 0.01) ionic strength depress the Tm of poly(A-U) and poly [d(A-T)] by as much as 28 and 22 degrees C, respectively. Longer double helices, poly(A . U) and Clostridium perfringens DNA are also denatured by the helix-destabilizing protein, but at relatively slow rates. The binding of this protein to [3H]-poly(U) on nitrocellulose filters in [Na+]-dependent, with a 50% reduction at 0.09 M NaCl. Based on its effect on the circular dichroism spectrum of poly(A), the protein was shown to distort the conformation of the polynucleotide chain. An analogous protein from mammalian cells, P8, was also shown to depress poly(A-U) Tm.

Physical studies of the interaction of a calf thymus helix-destablizing protein with nucleic acids.

UP1, a calf thymus protein that destabilizes both DNA and RNA helices, dramatically accelerates the conversion of the inactive conformers of several small RNA molecules to their biologically active forms [Karpel, R. L., Swistel, D. G., Miller, N. S., Geroch, M. E., Lu, C., & Fresco, J. R. (1974) Brookhaven Symp. Biol. 26, 165-174]. Using circular dichroic and spectrophotometric methods, we have studied the interaction of this protein with a variety of synthetic polynucleotides and yeast tRNA3Leu. As judged by perturbations in polynucleotide ellipticity or ultraviolet absorbance, the secondary structures of the single-stranded helices poly(A) and poly(C), as well as the double-stranded helices poly[d(A-T)] and poly(U.U), are largely destroyed upon interaction with UP1 at low ionic strength. This effect can be reversed by an increase in [Na+]: half the UP1-induced perturbation of the poly(A) CD spectrum is removed at 0.05 M Na+. The variation of poly(A) ellipticity and ultraviolet absorbance with [UP1]/[poly(A)]p is used to determine the length of single-stranded polynucleotide chain covered by the protein: 7 +/- 1 residues. A model is presented in which the specificity of UP1 for single strands and their concomitant distortion are a consequence of maximal binding of nucleic acid phosphates to a unique matrix of basic residues on the protein. Analogous to the effect on polynucleotides, UP1-facilitated renaturation of yeast tRNA3Leu follows the partial destruction of the inactive tRNA's secondary structure. At the tRNA absorbance maximum, UP1 effects a hyperchromic change of 10%, representing one-third of the secondary structure of the inactive conformer. This change is also clearly observable as a perturbation of the tRNA's circular dichroism spectrum.

Pigmentation phenotype instability in Myxococcus xanthus.

Cells of Myxococcus xanthus FB2 produce tan or yellow colonies. Subcultures of tan colonies yielded tan and yellow colonies and subcultures of most yellow colonies yielded only yellow colonies. Strain FB2 variants in which the color type is more stable were obtained. Yellow cells were distinguishable from tan by the presence of pigment(s) with an absorption maximum at 379 nm. Fluctuation Test experiments and the presence of this pigment(s) in liquid cultures of FB2 indicated that tan phenotype cells spontaneously became or segregated yellow cells in liquid culture. The frequency of appearance of yellow cells was increased in low density cultures (less than 10(6)/ml). The increase cannot be explained by differences in growth rates of the two phenotypes. No evidence that cell-cell contact or culture medium constituents affect the appearance of the yellow phenotype was found. Ultraviolet irradiation of FB2 resulted in an increased proportion of cells producing yellow colonies among the survivors. Greater UV resistance of yellow cells and UV-induced conversion of tan to yellow accounts for this increase. Low level photoreactivation of viability and of the tan phenotype occurred. Incubation of FB2 in medium containing mitomycin C, nalidixic acid, phenethyl alcohol, or at 36.5 degrees C also resulted in conversion of tan to yellow cells.

Intracellular, periodic structures in the gliding bacterium Myxococcus xanthus.

Electron microscopic observations of thin sections of Myxococcus xanthus vegetative cells revealed the presence of cytoplasmic bundles of 4- to 5-nm-diameter filaments running longtitudinally below the cell membrane and terminating in association with the envelope near one pole. Part of each bundle demonstrated a herringbone-like periodicity (approximately 12-nm spacing). This structure was observed in cells from shake cultures and in gliding cells fixed by several methods. It is proposed that the structure may be attached to the envelope near both poles in gliding cells and that the motive force for motility may be provided by its contraction and relaxation. In one of four nongliding mutants examined, the periodicity was indistinct or lacking. In this mutant another structure, comprised of linearly arrayed beads, was observed in association with the filamentous bundle. Another structure, characterized by major, transverse bands (approximately 34 nm apart), occurred in patches that may traverse the diameter of the wild-type cells in which the structure was observed.