The prostate anesthetic block for outpatient prostate surgery

Four patients with systemic autoimmune disorders, 3 of a serious nature, presented to 1 cardiologist over a 20-month span. In 3 of these cases, an HMG-CoA reductase inhibitor was presumably etiologic, while in the fourth case, the HMG-CoA reductase inhibitor might have unmasked the disorder. It would be useful to determine the true frequency of this complication, particularly in older patients not included in most of the statin trials to date. It is well established that autoimmune phenomena and particularly the development of autoantibodies increase with age. The data presented in this report that the group of HMG-CoA reductase inhibitors could be a heretofore poorly recognized etiologic agent. This issue might be addressed by a case-control study looking at the prevalence of statin use in elderly patients with systemic autoimmune disorders and in controls. Until then, the authors advise caution in the use of this class of medications in patient subgroups for whom no clear-cut clinical benefit has yet been proven.     

Selective stimulation of jugular ganglion afferent neurons in guinea pig airways by hypertonic saline

We evaluated the ability of hyperosmolar stimuli to activate afferent nerves in the guinea pig trachea and main bronchi and investigated the neural pathways involved. By using electrophysiological techniques, studies in vitro examined the effect of hyperosmolar solutions of sodium chloride (hypertonic saline) on guinea pig airway afferent nerve endings arising from either vagal nodose or jugular ganglia. The data reveal a differential sensitivity of airway afferent neurons to activation with hypertonic saline. Afferent fibers (both A delta and C fibers) with cell bodies located in jugular ganglia were much more sensitive to stimulation with hypertonic saline, compared with afferent neurons with cell bodies located in nodose ganglia. Additional studies in vivo demonstrated that inhalation of aerosols of hypertonic saline induced plasma extravasation in guinea pig trachea that was mediated via tachykinin NK1 receptors. Identification of a differential sensitivity of guinea pig airway afferent nerves to hypertonic saline leads to the speculation that airway responses to hyperosmolar stimuli may result from activation of afferent neurons originating predominantly from the jugular ganglion.     

Regulators of G protein signaling (RGS) proteins constitutively activate Gbeta gamma-gated potassium channels

Here we report novel effects of regulators of G protein signaling (RGS) on G protein-regulated ion channels. RGS3 and RGS4 induced a substantial increase in currents through the Gbeta gamma-regulated inwardly rectifying K+ channels, IK(ACh), in the absence of receptor activation. Concomitantly, the amount of current that could be activated by agonist was reduced. Pretreatment with pertussis toxin or a muscarinic receptor antagonist abolished agonist-induced currents but did not modify RGS effects. Cotransfection of cells with a Gbetagamma-binding protein significantly reduced the RGS4-induced basal IK(ACh) currents. The RGS proteins also modified the properties of another Gbeta gamma effector, the N-type Ca2+ channels. These observations strongly suggest that RGS proteins increase the availability of Gbeta gamma in addition to their previously described GTPase-activating function.     

Effect of PDE4 inhibitors on zymosan-induced IL-8 release from human neutrophils: synergism with prostanoids and salbutamol

1. The activation of neutrophils with particulate stimuli such as zymosan induces the generation of the C-X-C chemokine interleukin (IL)-8. There is evidence that neutrophil derived IL-8 plays an important role in human diseases such as the adult respiratory distress syndrome. In the present study, we examined the effects of cyclic AMP elevating agents on the ability of human neutrophils to generate IL-8 in response to zymosan particles. 2. The PDE4 inhibitor rolipram had limited effect on zymosan-induced IL-8 generation. In contrast, the PDE4 inhibitors RP 73401 and SB 207499 concentration-dependently suppressed IL-8 generation. The potency of these inhibitors was RP 73401 > SB 207499 > rolipram which is correlated with their rank order of potency at inhibiting the catalytic site of purified neutrophil PDE4. Pretreatment of neutrophils with the PDE3 inhibitor ORG 9935 or the PDE5 inhibitor zaprinast had no effect on IL-8 generation. 3. The prostanoids prostaglandin E1 (PGE1) and PGE2 inhibited zymosan-induced IL-8 release from neutrophils in a dose-dependent manner, in response to 10(-5) M PGE1 and PGE2 inhibiting IL-8 generation by 89% and 75%, respectively. Similarly, the beta2-adrenoceptor agonist salbutamol also inhibited IL-8 generation, but it was less effective than the prostanoids. 4. Significant synergism between prostanoids or salbutamol and the PDE4 inhibitors to inhibit IL-8 generation was observed. In contrast, there was no significant synergism between PGE2 and the PDE3 inhibitor ORG 9935 or the PDE5 inhibitor zaprinast. 5. In order to evaluate the potential role of protein kinase A in mediating the inhibitory effects of cyclic AMP-elevating agents, we used the protein kinase A inhibitors, H 89 and KT 5720. Pretreatment of neutrophils with these drugs completely reversed the inhibitory effects of a combination treatment with rolipram and PGE2 on zymosan-induced IL-8 release. 6. Microscopic examination revealed that most neutrophils contained one or more zymosan particles and that combination treatment with rolipram and PGE2 noticeably reduced the number of ingested particles. Moreover, there was a significant reduction in the percentage of neutrophils which ingested three or more zymosan particles. 7. Thus, our results demonstrate that cyclic AMP-elevating agents modulate the ability of neutrophils to generate IL-8 in response to a particulate stimulus. However, these agents also modulate the ability of neutrophils to phagocytose zymosan particles. Whether this effect will translate into inhibition of the ability of neutrophils to deal with infectious agents needs to be investigated further.     

Hyperglycemia induces apoptosis in pre-implantation embryos through cell death effector pathways

Although perinatal mortality rates have improved for pregnant diabetic women because of insulin therapy and tight metabolic control, infants of diabetics still experience significantly higher rates of congenital malformations and spontaneous miscarriages compared with those of non-diabetic women. Our results here indicate that hyperglycemic conditions, either in vivo or in vitro, modulate the expression of an apoptosis regulatory gene as early as the pre-implantation blastocyst stage in the mouse. Apoptosis in the mammalian pre-implantation blastocyst is a normal process, thought to protect the early embryo by eliminating abnormal cells. Here we demonstrate that expression of Bax, a Bcl-2-like protein, is increased at the blastocyst stage in the presence of high concentrations of glucose, and that these changes correlate morphologically with increased DNA fragmentation. Expression of Bax and caspase are necessary for this in vitro glucose-induced apoptotic event, and ceramide is involved in mediating this embryotoxic effect of glucose. We also show that these apoptotic cellular changes can be prevented in vivo by treating hyperglycemic mice with insulin before and immediately after conception. These findings emphasize the importance of tight glycemic control in diabetic women at the earliest stages after conception.     

Microscopic and energy dipersive x-ray analysis of surface adaptation of dental cements to dental ceramic surfaces

The authors present a retrospective study on 30 patients with prosthetic graft infection. Included are 25 patients with aortic graft infection, three with infection of a femorodistal bypass and two with infected axillofemoral grafts. There were 23 isolated primary prosthetic graft infections and seven aorto-enteric fistulas. Treatment consisted of graft excision and replacement with cryopreserved arterial homografts, harvested from brain-death multi-organ donors. The in situ technique was used in 27 cases. Eight patients died postoperatively and two deaths were from allograft related complications. The operative mortality rate was 11% for isolated aortic graft sepsis and the early limb salvage rate was 100%. Persistent or recurrent infection was noted in two cases. The mean follow-up of the series was 24.5 months and occlusive complications occurred in five patients (23%), which resulted in two major amputations. Serial CT scans showed abnormalities in six of the 22 survivors, all of them related to the aortic segment of the allograft. It is concluded that in situ reconstruction with cryopreserved arterial allografts represents an acceptable alternative, especially in the treatment of isolated aortic graft sepsis. Continued follow-up towards late deterioration and/or occlusive complications remains mandatory.     

Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to oxidize alpha-amino acids to a family of reactive aldehydes. Mechanistic studies identifying labile intermediates along the reaction pathway

We have recently demonstrated that neutrophils oxidize nearly all of the amino acids commonly found in plasma to a corresponding family of aldehydes in high yield. The reaction is mediated by hypochlorous acid (HOCl), the major oxidant generated by the myeloperoxidase-H2O2-Cl- system of phagocytes. We now present evidence for the underlying mechanism of this reaction, including the structural requirements and reaction intermediates formed. Utilizing mass spectrometry and isotopically labeled amino acids, we rule out hydrogen atom abstraction from the alpha-carbon as the initial event in aldehyde formation during amino acid oxidation, a pathway known to occur with ionizing radiation. Aldehyde generation from amino acids required the presence of an alpha-amino moiety; beta- and epsilon-amino acids did not form aldehydes upon oxidation by either the myeloperoxidase system or HOCl, generating stable monochloramines instead. UV difference spectroscopy, high pressure liquid chromatography, and multinuclear (1H,15N) NMR spectroscopy established that the conversion of alpha-amino acids into aldehydes begins with generation of an unstable alpha-monochloramine, which subsequently decomposes to yield an aldehyde. Precursor product relationships between alpha-amino acid and alpha-monochloramine, and alpha-monochloramine and aldehyde were confirmed by high pressure liquid chromatography purification of the reaction intermediate and subsequent 1H and 15N NMR spectroscopy. Collectively, these results detail the chemical mechanism and reaction intermediates generated during conversion of amino acids into aldehydes by myeloperoxidase-generated HOCl.     

Genetic analysis of Shigella sonnei form I antigen: identification of a novel IS630 as an essential element for the form I antigen expression

The form I coding region of Shigella sonnei was cloned and shown to have an operon-like rfb organization. It was found that the 11.0 kb HindIII-XbaI fragment of pHH201 encoding the form I antigen contains 10 contiguous open reading frames (ORF), ORF1 to ORF10. Deletions from either end of pHH201, within ORF1 or ORF10, eliminated form I expression. ORF1 and ORF2 share significant nucleic and amino acids homologies to two ORF's of the Salmonella typhi Vi antigen genes. ORF5 in pHH201 is identical to IS630. pHH2064, derived from pHH201, lacks the IS630 element and can stably express the form I antigen inE. coli HB101. However, pHH2064 is structurally unstable in a S. sonnei form II host. This indicates that the presence of the IS630 gene within the S. sonnei rfb operon may be necessary for the stability of form I expression in S. sonnei. This finding is substantiated by the observation that all virulent S. sonnei isolates examined in this study retained the IS630 element within their rfb operon.     

Segmental right ventricular function after acute myocardial infarction: two-dimensional echocardiographic study in 63 patients

Right ventricular (RV) segmental contraction was studied in 63 patients with acute myocardial infarction (MI), using 2-dimensional (2-D) echocardiography. Group A included 32 patients with ischemic RV dysfunction: 19 had a disproportionate increase in right atrial pressure at the time of the examination (Group AI) and in 13 patients, right atrial pressure was normal when the echocardiogram was obtained (Group AII). Group B included 31 patients without ischemic RV dysfunction. Alkinesia or dyskinesia of the RV wall was found in 30 patients: 19 from Group AI, 8 from Group AII, and 3 from Group B. Asynergy could be identified in all segments of the RV wall including the outflow tract, RV apex, and anterior wall, but was more frequently found in the posterior wall (29 patients), best seen in the transversal subcostal short-axis view. A significant difference was found either in the frequency of wall motion abnormalities or in the number of segments with asynergy among the 3 groups (p less than 0.001). However, asynergy of the RV wall may be present in some patients with normal right heart hemodynamic function, suggesting that asynergy may be more sensitive than hemodynamic function in the diagnosis of acute RV infarction. Paradoxical septal motion was found in 8 patients, all in Group AI, and all had a right atrial pressure equal to or greater than pulmonary capillary pressure.