Effects of different speeds of induction with sevoflurane on the EEG in Man

The effects of two kinds of induction speed of sevoflurane anesthesia on the EEG pattern were compared in the same individual using medical student volunteers: a first exposure of 4% was given, followed after full recovery, by incremental doses of 1, 2 and 4% successively, each being administered for 10min. The arterial blood level of the anesthetic was measured using gaschromatograph. The changes of EEG pattern during fast induction with 4% were not represented by the abbreviation of those observed during the slow induction with the incremental doses. The administration of 4% induced a sudden appearance of high voltage, rhythmic slow waves of 2–3Hz at 1–3min when the arterial blood anesthetic level increased maximally, which was then followed by a pattern of faster activities of 10–14Hz mixed with 5–8Hz slow waves. In contrast, the administration of incremental doses induced an increase in frequency and amplitude of EEG activities in the light plane, followed by their decreases in deeper planes. The final EEG patterns were identical for both these methods of induction. These findings confirmed our previous hypothesis that not only the arterial blood level of anesthetics but the rate of its increase are important factors determining the EEG pattern of anesthesia.(Avramov MN et al.: Effects of different speeds of induction with sevoflurane on the EEG in man. J Anesth 1: 1–7, 1987)     

Anabolic actions of PTH in murine models: two decades of insights

Parathyroid hormone (PTH) is produced by the parathyroid glands in response to low serum calcium concentrations where it targets bones, kidneys, and indirectly, intestines. The N-terminus of PTH has been investigated for decades for its ability to stimulate bone formation when administered intermittently (iPTH) and is used clinically as an effective anabolic agent for the treatment of osteoporosis. Despite great interest in iPTH and its clinical use, the mechanisms of PTH action remain complicated and not fully defined. More than 70 gene targets in more than 90 murine models have been utilized to better understand PTH anabolic actions. Because murine studies utilized wild-type mice as positive controls, a variety of variables were analyzed to better understand the optimal conditions under which iPTH functions. The greatest responses to iPTH were in male mice, with treatment starting later than 12 weeks of age, a treatment duration lasting 5–6 weeks, and a PTH dose of 30–60 μg/kg/day. This comprehensive study also evaluated these genetic models relative to the bone formative actions with a primary focus on the trabecular compartment revealing trends in critical genes and gene families relevant for PTH anabolic actions. The summation of these data revealed the gene deletions with the greatest increase in trabecular bone volume in response to iPTH. These included PTH and 1-α-hydroxylase (Pth;1α(OH)ase, 62-fold), amphiregulin (Areg, 15.8-fold), and PTH related protein (Pthrp, 10.2-fold). The deletions with the greatest inhibition of the anabolic response include deletions of: proteoglycan 4 (Prg4, −9.7-fold), low-density lipoprotein receptor-related protein 6 (Lrp6, 1.3-fold), and low-density lipoprotein receptor-related protein 5 (Lrp5, −1.0-fold). Anabolic actions of iPTH were broadly affected via multiple and diverse genes. This data provides critical insight for future research and development, as well as application to human therapeutics. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

99mTc-MIBI scan in mammary Pagets disease: a case report

Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) uptake is known to be increased in breast cancer because of increased blood flow from angiogenesis and heightened metabolism. We performed a 99mTc-MIBI scan in a patient with mammary Paget's disease. The patient had underlying invasive cancer in the same side of the breast. 99mTc-MIBI scan exhibited a scintigraphic image of the uptake from the invasive cancer lesion located deeply in the breast toward the epidermis. 99mTc-MIBI showed an uptake in the deeply located invasive cancer lesion as well as nipple lesion. Especially, the delayed phase of Tc-MIBI scan demonstrated the tumor site more accurately. In conclusion, 99mTc-MIBI scan could be a useful adjunct to clinical decision making in the management of Paget's disease of the breast.     

Antitumor effect of trimelamol against human breast carcinoma xenografts in nude mice

The antitumor effect of N-2, N-4, N-6-trihydroxymethyl-N-2, N-4, N-6-trimethylmelamine (trimelamol), a synthetic analogue of hexamethylmelamine, was investigated using human breast carcinoma xenografts in nude mice. Four tumor models, T-61, Br-10, R-27 and MCF-7 were estrogen receptor (ER)-positive and their growth was estradiol-dependent. The MX-1 model was ER-negative and grew estradiol-independently. Sixty mg of trimelamol per kg dissolved in 5% dimethylsulphoxide (DMSO) with 5% glucose was administered intraperitoneally for 5 days weekly for three weeks. Trimelamol showed potent antitumor activity on T-61 and MX-1 in a dose-responsive manner with a marginal effect on Br-10, whilst R-27 and MCF-7 were insensitive to this agent. This antitumor spectrum on human breast carcinoma xenografts was similar to that of hexamethylmelamine previously reported using the same xenograft models. Trimelamol is water-soluble and does not require metabolic activation which is needed for hexamethylmelamine. These advantages allow the paraenteral administration of trimelamol, and warrant the further investigation of this drug for breast carcinomas.     

Catecholamine Release caused by Carbon Dioxide Insufflation during Laparoscopic Surgery

Purpose

We evaluated plasma catecholamine levels during pneumoperitoneum in laparoscopic surgery.

Materials and Methods

Plasma epinephrine and norepinephrine were evaluated in 29 patients who underwent laparoscopic retroperitoneal surgery in a half lateral decubitus position (group 1) or laparoscopic varicocelectomy in a Trendelenburg position (group 2).

Results

The levels of epinephrine and norepinephrine increased significantly 5 minutes after carbon dioxide insufflation compared to levels after Veress needle insertion and just before insufflation. The elevation of catecholamine levels during laparoscopic procedures was greater in group 1.

Conclusions

Our results indicate that carbon dioxide insufflation may cause catecholamine release during laparoscopic surgery. Careful monitoring of hemodynamics is mandatory at the beginning of the procedure.     

Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole.

Fluoromisonidazole (FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant oxygen levels. When labeled with the positron emitter fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (PETT). This paper presents the first experiences with PETT imaging of [F-18]FMISO uptake in human malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected cancers were imaged prior to primary radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-radiotherapy studies revealed retention of [F-18]FMISO in tumors that significantly exceeded plasma concentrations by 2 hr after drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18] FMISO PETT images is presented, defining hypoxic elements within a tumor volume as regions with a threshold regional tumor:plasma [F-18]FMISO ratio of greater than or equal to 1.4 by 2 or more hours after injection. Toward the end of a course of fractionated radiotherapy, three repeat studies in patients with initially positive scans showed no tumor accumulation of drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]FMISO as a safe hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with tumor outcome, [F-18]FMISO PETT imaging may be developed as a predictor of tumor response to conventional radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.     

Tumor colony formation by Friend virus-infected cells in immunosuppressed mice.

We have investigated the role of host immunological factors in the formation of "tumor colonies" in the spleens of unirradiated C57BL/6 X C3Hf/Bi FI mice 9 days after i.v. injection of spleen cells from Friend virus (FV)-infected C3Hf/Bi donors. Pretreatment of hosts with antilymphocyte serum (ATS) increased the number of tumor colonies. Pretreatment with formalinized FV-infected cells had the opposite effect, and ATS diminished the inhibitory effect of preimmunization. Cell suspensions from 11 individual FV-infected donors were examined. The suspensions differed with respect to their behavior on transplantation into untreated and ATS-pretreated F1 hybrid hosts. With several suspensions, the number of tumor colonies produced was approximately proportional to the number of cells injected; in all of these, ATS increased the slope of the line relating colony number to cell number. With most of the suspensions, tumor colony-forming efficiencies in untreated hosts strikingly decreased with increasing number of cells injected; ATS induced an increase in the number of tumor colonies and rendered the colony-forming response more nearly proportional to cell number. With two suspensions, few or no colonies developed; pretreatment with ATS had no significant effect. When the 11 cell suspensions were considered together, a proportional relation was found between the magnitude of the ATS effect (i.e., colony number in the presence of ATS minus colony number in the absence of ATS) and the colony-forming efficiency in ATS-treated mice. The ATS effect on the average was equivalent to a 2-fold increase in tumor colony-forming efficiency. We interpret these findings to indicate that two factors interact to determine the number of tumor colonies produced by spleen cells from FV-infected C3H donors in untreated F1 hybrid hosts. One is a property of the FV-infected cell population and includes its frequency of tumor colony-forming units; this factor varies widely among different cell suspensions. The other is a property of the tumor colony-forming units-host interrelationship and includes the vulnerability of tumor colony-forming units to the host immune response elicited by the injected cells; this factor appears to be constant with different cell suspensions. The present results show that the two factors can be dissociated in immunosuppressed hosts.     

Changes in expression of sodium cotransporters and aquaporin-2 during ischemia-reperfusion injury in rabbit kidney

Ischemic renal injury is associated with defects in transport functions of the proximal tubules and urinary concentration ability. To determine whether alterations in expression of various transporter genes contribute to an impairment in renal functions, the expression of various solute transport genes was analyzed in renal cortex and medulla of rabbits with ischemic acute renal failure. Rabbits were subjected to 60 min of renal pedicle clamping followed by 24, 48, or 72 h of reperfusion. Urine volume and glomerular filtration rate were markedly decreased, which were accompanied by an increase in serum creatinine level and fraction Na+ excretion. Glucosuria and phosphaturia were evident during reperfusion periods. These alterations in renal functions were persisted to 72 h after reperfusion. The Na+-dependent uptakes of glucose and phosphate by brush border membrane vesicles were inhibited by 24 h of reperfusion. mRNA levels for Na+-glucose, Na+-phosphate, and Na+-succinate cotransporter analyzed by RT-PCR were not changed by 60 min of ischemia alone, but were significantly reduced by 24 h of reperfusion. mRNA levels for apical Na+-K+-2Cl- cotransporter, NaCl cotransporter, and turea transporter in the medulla were not changed during reperfusion. Protein levels for AQP2 in the medulla, but not AQP1 in the cortex, analyzed by Western blot were significantly reduced at 24 h after reperfusion. These results suggest that reductions in expression of Na+-cotransporter genes in the proximal tubules may be important factors in the impairment in Na+-dependent reabsorption of solutes and that decrease in AQP2 protein may be involved in defect in urinary concentration ability in rabbits with ischemic acute renal failure.