Estimated affinity of isoproterenol to cardiac chronotropic beta-receptor and of phenylephrine to vasoconstrictive alpha-receptor of the systemic resistance vessels in human borderline hypertension

There has been yet no report, to our knowledge, which clarified the affinity ("sensitivity") of catecholamines to cardiac chronotropic beta-adrenergic receptor or to vasoconstrictive alpha-adrenergic receptor of skeletal muscle resistance vessels in human borderline hypertension (BHT), using an analysis of the kinetics of the drug-receptor interaction. In the first half of this study, isoproterenol (ISO) infusion test was performed on "normal" subjects (n = 12) and subjects with BHT (n = 10). Dose-response relation was obtained in terms of various doses of ISO and the increments of heart rate (deltaHR) produced by ISO. In the latter half of this study, phenylephrine (PHE) infusion test was carried out in the series of "normal" subjects (n = 5) and subjects with BHT (n = 6), a partly different series from the first series of subjects. Dose-response relation, again, was obtained in terms of various doses of PHE and the increments of total peripheral resistance (deltaTPR) produced by PHE. These relations were displayed on Lineweaver-Burk's plot and the "affinity" of ISO to cardiac chronotropic beta-receptor or that of PHE to vasoconstrictive alpha-receptor of skeletal muscle resistance vessels was estimated, graphically, assuming that 1) drugs were diluted by a volume of body fluid equal to the blood volume which was actually measured in each individual and 2) this concentration of drugs existed around the receptor site, i.e., there was no significant individual variations in terms of the metabolism and the distribution of the drugs. Estimated "affinity" of ISO to cardiac chronotropic beta-receptor was 0.168 +/- 0.014 x 10(4) ml X ug-1 (mean +/- SE, n = 10) in patients with BHT, while it was 0.170 +/- 0.015 x 10(4) (n = 12) in "normal" subjects. Estimated "affinity" of PHE to vasoconstrictive alpha-receptor of skeletal muscle resistance vessels was 0.171 +/- 0.011 x 10(2) ml X ug-1 (n = 6) in patients with BHT, while it was 0.183 +/- 0.012 x 10(2) (n = 5) in "normal" subjects. It is concluded from these data, almost fairly, that there is no difference in terms of the estimated "affinity" of ISO to cardiac chronotropic beta-receptor or that of PHE to vasoconstrictive alpha-receptor between "normal" subjects and patients with BHT. It was also found, in PHE infusion tests, that the plasma adrenaline concentration was significantly higher in patients with BHT than in "normal" subjects, at least at two points of time in the test: a) immediately before PHE infusion, when every individual appeared to be considerably restful and b) at the end of 1-2 min after the completion of the infusion of the largest dose of PHE used.     

Effects of isoflurane and halothane on the calcium ion-tension curve in rat myocardium

In order to clarify the interaction of volatile anesthetics and extracellular calcium ion on the myocardial contraction, effects of both isoflurane (1.0%) and halothane (0.5%) on the extracellular calcium ion concentration ([Ca²⁺]_O)-tension curve were studied. Increasing [Ca²⁺]_O enhanced the myocardial contraction response, and the maximal response was obtained at [Ca²⁺]_O of 3.0mM. Halothane depressed the maximal value of the tension development in response to increasing [Ca²⁺]_O, while isoflurane did not (P 0.01). The probit response of the developed tension to the changes in [Ca²⁺]_O indicated that isoflurane increased the median effective concentration (EC₅₀) of [Ca²⁺]_O significantly from 0.484 ± 0.051 (mean ± SEM) to 0.870 ± 0.056mM (P = 0.001), but halothane did not (P = 0.018). Therefore, 1.0% isoflurane was concluded to move the [Ca²⁺]_O-tension curve to the right, while a downwards shift occurred with 0.5% halothane.(Saeki S, Hirakawa M, Shimosato S: Effects of Isoflurane and Halothane on the Calcium Ion-tension Curve in Rat Myocardium. J Anesth 6: 172–175, 1992)     

Changes in local cerebral blood flow, glucose utilization, and mitochondrial function following traumatic brain injury in rats

The pathophysiology of secondary brain damage following experimental traumatic brain injury was investigated by measuring local cerebral blood flow (lCBF), local cerebral glucose utilization (lCGU), and activity of succinate dehydrogenase (SDH), which is a mitochondrial enzyme of the tricarboxylic acid cycle, in the rat brain after moderate lateral fluid percussion injury. Measurements used autoradiography for lCBF and lCGU with [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. Regional SDH activity was determined using quantitative imaging of formazan produced from 2,3,5-triphenyl tetrazolium chloride by SDH. lCBF decreased at 1 hour after injury and was significantly lower than the preinjury level in almost all regions of both hemispheres at 6 and 24 hours, and remained low at 2 weeks. lCGU increased 1 hour after injury but was significantly decreased at 6 and 24 hours, and at 2 weeks in most regions of both hemispheres. The ipsilateral hemisphere showed a significant decrease in the activity of SDH in the cortices, hippocampus, thalamus, and caudate/putamen, most conspicuously 72 hours after injury, whereas no significant decrease was observed in the contralateral hemisphere at any time. Necrosis in the injured cortex and reduction of the number of neurons in the ipsilateral hippocampus were observed 2 weeks after injury. The present study showed that a decrease in lCBF and mitochondrial dysfunction occur with glucose hypermetabolism around 1 hour after lateral fluid percussion injury, and that lCBF, lCGU, and mitochondrial function all deteriorate after 6 hours. This suggests that lCBF and cellular metabolism may change dynamically during the several hours following traumatic brain injury, and afterwards neuronal damage may result in an irreversible change in the areas with depressed glucose hypermetabolism in the early period after injury in combination with mitochondrial dysfunction.     

De novo uterine sarcoma with good response to neo-adjuvant chemotherapy

Abstract.  Numa F, Umayahara K, Ogata H, Nawata S, Sakaguchi Y, Emoto T, Kawasaki K, Hirakawa H, Sase M, Oga A, Kato H. De novo uterine sarcoma with good response to neoadjuvant chemotherapy. We report here the extremely rare case of a 28-year-old woman with advanced stage uterine sarcoma arising soon after a cesarean section. She underwent an abdominal cesarean section because of a breech presentation. At the time of the procedure, there were no abnormal findings such as leiomyoma of the uterus in the abdominal cavity. One year later, she was referred to our hospital because of a large abdominal tumor. Transabdominal power Doppler ultrasonography and magnetic resonance imaging (MRI) showed a large hypervascular tumor in the abdominal cavity. Her serum levels, for the two tumor markers carbohydrate antigen CA125 and LDH, were elevated, at 219 U/ml (< 35 U/ml) and 862 IU/l (115 U/ml−217 U/ml), respectively. On the basis of a diagnosis of malignant tumor of gynecological origin, exploratory laparotomy was performed, and through biopsy, the tumor was found to be advanced undifferentiated uterine sarcoma. She exhibited a good response to neoadjuvant chemotherapy consisting of cisplatin, epirubicin, and dimethyltriazenoimidazole carboxamide (DTIC) every 28 days, which was successfully followed by a hysterectomy.     

Day surgery for pediatric inguinal hernia repair

Pediatric patients with inguinal hernia can be good candidates for day surgery. Since 1986, 1273 such patients have been treated under our day surgery system. Although 8 patients (0.6%) were unable to go home after surgery due to perioperative complications and 21 (1.6%) visited earlier than scheduled after discharge, no major complications were noted and postoperative complications did not differ from those seen in the inpatient setting. Our questionnaire survey demonstrated that 96% of the families were satisfied with the system. Based on our own experience and a literature review of day surgery for inguinal hernia repair in children, the problems surrounding the day care system are discussed. Patient selection, preoperative assessment, general anesthesia, postoperative care including oral intake and analgesia, and postoperative follow-up are considered the most important issues in the day care system. A team approach including pediatric surgeons, anesthesiologists, and pediatric nurses is considered indispensable for the safe and satisfactory day surgery treatment.     

Infrequent Mutations of the hOGG1 Gene, That Is Involved in the Excision of 8-Hydroxyguanine in Damaged DNA, in Human Gastric Cancer

DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh⁸Gua), which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9 gastric cancer cell lines and 35 primary gastric cancers for mutations and genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single strand conformation polymorphism analysis. A G-to-A transition was detected in a gastric cancer cell line, MKN1. This nucleotide change caused the conversion of the amino acid from Arg to His at codon 154, which is located in a domain highly conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected in primary gastric cancers. We compared the distribution of the polymorphic alleles associated with enzymatic activity (hOGG1-Ser³²⁶ vs. hOGG1-Cys³²⁶) between 35 gastric cancer patients and 42 healthy individuals. Although the frequency of the Cys³²⁶ allele, associated with low enzymatic activity, in gastric cancer patients was a little higher than that in healthy individuals, the difference did not reach statistical significance. These results suggest that low hOGG1 activity due to mutations and genetic polymorphisms is involved in the development of only a small subset of gastric cancers.     

Somatic mutations of epidermal growth factor receptor in colorectal carcinoma.

PURPOSE: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non-small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA. EXPERIMENTAL DESIGN: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA. RESULTS: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma. CONCLUSIONS: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment.     

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor

We report a case of adenosquamous carcinoma of the stomach that produced granulocyte-colony stimulating factor (G-CSF). The patient, who had an admission diagnosis of advanced gastric cancer, had marked leukocytosis without evidence of infection. After leukemia and metastatic leukemoid reaction were excluded by bone marrow examination, a G-CSF-producing cancer was suspected as the cause of the abnormally elevated serum G-CSF level. The resected stomach tumor was histologically diagnosed as adenosquamous carcinoma; positive expression of G-CSF by tumor cells was shown with immunohistochemical detection, which confirmed the preoperative diagnosis. Recurrent disease in the liver and lymph nodes, accompanied by leukocytosis and re-elevation of serum G-CSF, developed just 3 months after the curative gastrectomy and adjuvant chemotherapy. All of the recurrent disease was resected, restoring normal levels of serum G-CSF. The patient survived for almost 2 years after the initial surgery with extensive chemotherapy, including weekly treatment with paclitaxel, before finally succumbing to liver failure secondary to extensive liver metastasis.