Phenobarbital following phototherapy for Crigler-Najjar syndrome type II with good fetal outcome: a case report.

In the presence of severe hyperbilirubinemia in Crigler-Najjar syndrome Type II, a fetus is at risk for kernicterus. A 34-year-old woman, gravida 4, para 1, with Crigler-Najjar syndrome Type II was treated with phenobarbital administration following phototherapy during each of 2 pregnancies. Both infants were healthy and developed normally.

Immature brain injury via peroxynitrite production induced by inducible nitric oxide synthase after hypoxia-ischemia in rats.

OBJECTIVE: To determine whether, and if so how, iNOS expresses and affects brain injury induced by hypoxia-ischemia in an immature brain. MATERIAL AND METHODS: Seven-day-old Wistar rat pups were exposed to right common carotid artery ligation followed by 1.5 hours of hypoxia. The time course of iNOS mRNA expression, enzymatic activity, and protein production in the cerebral cortex were determined. The extent of the infarct area in the cerebral cortex and the production of 3-nitrotyrosine (a biomarker of peroxynitrite) were compared between the control pups and pups treated with S-methyl-isothiourea (a selective iNOS inhibitor). RESULTS: In the cortex ipsilateral to carotid ligation, iNOS mRNA appeared from 6 hours to 24 hours after hypoxia-ischemia and disappeared at 48 hours. The iNOS protein and its activity also increased at 12 hours and reached a maximum level at 48 hours after the insult. The percentage of damage in the cerebral cortex was significantly higher in the control pups than in treated pups (31.9 vs 10.6%). Tri-nitrotyrosine following iNOS expression-positive cells were located predominantly at the infarct and peri-infarct regions. CONCLUSIONS: iNOS expression might be an important determinant of ischemic immature brain injury.

Repetitive intermittent hypoxia-ischemia and brain damage in neonatal rats.

OBJECTIVE: To know the effect of brief-repetitive intermittent hypoxia-ischemia on the development of perinatal brain damage. STUDY DESIGN: Seven-day-old Wistar rats underwent ligation of the unilateral common carotid artery. The animals were allocated to three groups (n=12 in each group) and exposed to 8% oxygen as follows: group A: continuous exposure for 180 min; group B: continuous exposure for 90 min; and group C: 10 min of exposure repeated at 10-min intervals over a period of 180 min (total exposure time, 90 min). Seventy-two hours after exposure to hypoxia, the cerebral cortex was examined to assess the degree of neuronal necrosis and brain damage was classified into four grades of severity, 0-3. To evaluate the extent of brain damage, we used immunohistochemical staining with TIB-128 antibody, which reacts to MAC-1 antigen specific to microglia, and observed the glial reaction in the cerebral cortex, hippocampus, thalamus, and striatum. RESULTS: All the brain damage observed in groups A-C occurred on the side where the ligation was performed. The most severe damage was found in group A animals, of which seven showed significant neuronal necrosis, having a grade 2 or more advanced lesion. In group B, neuronal necrosis was modest, with only one animal having a grade 2 lesion. In group C, a significant neuronal necrosis was found in six animals despite having the same period of hypoxic exposure as those in group B. MAC-1 positive cells appeared in the cerebral cortex of histologically damaged animals and extended to the hippocampus, thalamus, and striatum in severely damaged animals from groups A, B, and C. CONCLUSION: Examination of the neonatal rat model suggested that repetitive and intermittent, rather than continuous hypoxia-ischemia, causes pronounced damage in the immature brain.

ABC transporter genes, kasKLM, responsible for self-resistance of a kasugamycin producer strain.

We previously reported that a 7.6-kb DNA fragment from Streptomyces kasugaensis M338-M1, a kasugamycin (KSM) producer, included KSM acetyltransferase gene (kac338) and some other genes possibly involved in KSM biosynthesis. As an extension of that study, a 10-kb SacI-KpnI DNA fragment, located approximately 5-15-kb upstream of kac33, was cloned and a 4.2-kb SacI-EcoRI fragment therefrom was sequenced, revealing one incomplete (designated ORF J) and three complete open reading frames (designated kasK, kasL and kasM). The coding frames of kasK, L and M overlap one another with terminator/initiator ATGA sequence. RT-PCR analysis of a DNA region including kasKLM indicated the presence of one transcript that is long enough to span the three genes. The kasK gene potentially encodes an ATP-binding protein of the ATP-binding cassette (ABC) transporter superfamily. Homology search for the deduced KasK protein shows similarity to other ABC transporters involved in self-resistance of a mithramycin and possibly doxorubicin producer strain. The kasL and kasM genes encode different integral membrane proteins, both having six putative transmembrane helices. An expression plasmid for kasKLM (pTV-KLM) was constructed and these genes were expressed in E. coli JM 109, which had been sensitive to KSM. The transformant acquired resistance to KSM, suggesting that KasK, L and M proteins as a set in S. kasugaensis M338-M1 pump out KSM to protect the producer from its toxic metabolite.

The relationship between the response to external light stimulation and behavioral states in the human fetus: how it differs from vibroacoustic stimulation.

OBJECTIVE: To determine the effects of external light stimulation on fetal behavioral states and know the difference from those of vibroacoustic stimulation. METHODS: A flashlight and a vibroacoustic stimulator was applied directly on the maternal abdomen to determine the response of 56 normal fetuses at 36-40 weeks gestation. Fetal heart rate (FHR) and body movements were recorded using an actocardiograph, and fetal eye movements were observed using real-time ultrasonography. Using Nijhuis's criteria, the fetal behavioral states (1F-4F) were determined. FHR acceleration was considered a fetal response to the stimulations. RESULTS: The lag time between stimulation and fetal response was within 4 s. A positive response rate to the light stimulation was higher at behavioral states 2F (82%) and 3F (83%) than at state 1F (4%). Light stimulation changed the behavioral state of two of the six 3F fetuses (33%) from 3F to 4F. No change of state was observed in fetuses that were in states 1F and 2F. For vibroacoustic stimulation, fetal response was 100% positive and changes of states were observed frequently irrespective of the behavioral state before the stimulation. CONCLUSION: Fetal response to light stimulation is closely connected to fetal behavioral states and may reflect some distinct stages of the sleep-wakefulness cycle.

Placenta previa increta penetrating the entire thickness of the uterine myometrium: ultrasonographic and magnetic resonance imaging findings.

This is the first report of placenta previa increta in which the placenta villi penetrated the entire thickness of the uterine myometrium, but did not invade the pubocervical fascia. Ultrasonographic and magnetic resonance imaging findings are described.

Propofol does not affect the canine cardiac conduction system under autonomic blockade.

PURPOSE: To determine the effects of propofol on the cardiac conduction system in dogs with pharmacological autonomic blockade. METHODS: In eight mongrel dogs receiving 6 mg.kg-1.hr-1 propofol and vecuronium under pharmacological autonomic blockade with atropine and propranolol the infusion rates of propofol were increased from 6, (baseline), to 12, 18 and 24 mg.kg-1.hr-1 at 60-min intervals. An electrophysiological study assessed sinus rate, sinus node recovery time, corrected sinus node recovery time, intraatrial conduction time, AV nodal effective refractory period, Wenckebach cycle length and AV conduction times. Electrocardiographical variables and arterial pressures were also measured. All measurements were repeated at 30 min after the beginning of each infusion of propofol. RESULTS: Propofol did not produce direct effects on the electrophysiological or electrocardiographical variables at any infusion rates. Heart rates did not change at higher infusion rates in the presence of decreases in arterial pressures. CONCLUSION: Propofol did not affect the cardiac conduction system in the presence of autonomic blockade. Thus, the direct cardiac effects of propofol do not play a causative role in the genesis of propofol-associated bradyarrhythmias.

A 7.6kb DNA region from Streptomyces kasugaensis M338-M1 includes some genes responsible for kasugamycin biosynthesis.

A 7.6kb PstI-KpnI DNA fragment including a sequence highly similar to kasugamycin acetyltransferase gene (kac) was isolated from Streptomyces kasugaensis M338-M1 and sequenced. Nine open reading frames (ORFs), designated as ORF A, B, C, D, E, F, G, H and I, were recognized in this region, although ORF A was incomplete. ORF G runs in the opposite direction to the others. The amino acid sequence deduced from ORF H showed 98% similarity to that of the kasugamycin acetyltransferase from S. kasugaensis MB273-C4, another kasugamycin (KSM) producer. Transformation of E. coli JM109 with ORF H made the strain highly resistant to KSM. The deduced amino acid sequences of the ORF A, C and D products were similar, respectively, to glucosyltransferase I from E. coli (26%), beta-alanine: pyruvate transaminase from Pseudomonas putida (32%) and dTDP-D-glucose 4,6-dehydratase (StrE) from Streptomyces griseus (37%). The strE-like ORF (ORF D) seems to be the gene responsible for formation of the 6-deoxy structure of the kasugamine moiety. ORF A and ORF C are also likely to have roles in KSM biosynthesis. Taken together, our analyses strongly suggest that this DNA region includes at least a part of the gene cluster of KSM biosynthesis.

Effects of magnesium sulphate on the cardiovascular system, coronary circulation and myocardial metabolism in anaesthetized dogs.

We have studied the effects of i.v. bolus doses of magnesium sulphate (MgSO4) 60, 90 and 120 mg kg-1 on haemodynamic state, the coronary circulation and myocardial metabolism in nine dogs anaesthetized with pentobarbitone and fentanyl. MgSO4 produced dose-dependent decreases in arterial pressure, heart rate, left ventricular dP/dtmax and left ventricular minute work index (LVMWI) and an increase in the time constant of left ventricular isovolumic relaxation. Stroke volume increased, systemic vascular resistance decreased and cardiac output did not change significantly. MgSO4 produced decreases in coronary perfusion pressure, coronary vascular resistance and myocardial oxygen consumption (MVO2). Coronary sinus blood flow, lactate extraction ratio and the ratio of LVMWI to myocardial MVO2, that is an index of cardiac efficiency, did not change significantly. This study indicated that the depressant effect of MgSO4 on cardiac function was offset by lowering of peripheral vascular resistance, so that cardiac pump function remained effective, and the almost constant coronary sinus blood flow resulted from the decrease in coronary vascular resistance even at higher doses.

Inhibition of anchorage-independent growth of tumor cells by IT-62-B, a new anthracycline.

IT-62-B, a new anthracycline isolated from fermentation broths of Streptomyces sp. IT-62, reversed certain tumor cell phenotypes in vitro including some of human origin. The observed normal phenotypes were anchorage dependence of cell growth, flattened cell morphology and restoration of actin stress fibers. The extent of the anchorage dependence of cell growth induced by IT-62-B was generally greater than that by doxorubicin or pirarubicin. The cell-flattening effect of IT-62-B on cells of T24 (human bladder), but not on C-33A (human cervix), accompanied inhibition of fos gene expression. T24 cells, once flattened by IT-62-B, retained their flat morphology even in drug-free, fresh medium and eventually died in several days. IT-62-B, unlike doxorubicin, only slightly inhibited the topoisomerase II reaction in vitro and DNA synthesis in isolated cell nuclei.

Ultrasonographic findings in the periventricular region in premature newborns with antenatal periventricular leukomalacia.

Cranial ultrasonography was carried out at least three times a week during the first 16 days of life in all 53 premature newborns born within study period. If a cyst of more than three mm was detected in the periventricular region by fourteenth day of life, it was judged to be antenatal PVL. Periventricular echodensity was classified into mild, moderate or severe periventricular echodensity (PVE). Among 53 newborns, 11 babies (20.8%) were diagnosed as having antenatal PVL. Cysts were observed in the first two days in 9 cases (81.8%) out of 11 babies, and in bilateral periventricular regions in 8 cases (72.7%) out of 11 babies. All 3 babies with severe PVE in the periventricular region had PVL at the time of diagnosis or developed PVL shortely after severe PVE was detected.

Effects of magnesium sulphate on atrioventricular conduction times and surface electrocardiogram in dogs anaesthetized with sevoflurane.

We have studied the effects of magnesium on atrioventricular (AV) conduction times and surface electrocardiogram during both sinus rhythm and atrial pacing in seven dogs anaesthetized with 1 MAC of sevoflurane. A bolus dose of magnesium sulphate (MgSO4) 30, 60 and 90 mg kg-1 significantly increased plasma magnesium concentrations from 1.3 (SEM 0.1) to 15.3 (1.3) mg dl-1. MgSO4 significantly prolonged A-H (AV nodal conduction time during sinus rhythm), St-H (intra-atrial and AV nodal conduction time during atrial pacing) and H-S (total ventricular conduction time) intervals at doses > or = 30 mg kg-1 ; H-V interval (His-Purkinje conduction time) at doses > or = 60 mg kg-1; RR and PR intervals and QRS duration at doses > or = 30 mg kg-1 in a dose-related manner during both sinus rhythm and atrial pacing. QTc interval remained unchanged during sinus rhythm. The doses of MgSO4 used did not have deleterious effects on AV conduction times and surface electrocardiogram during 1 MAC of sevoflurane anaesthesia. This finding suggests that MgSO4 in high doses was safe and may be indicated for cardiac arrhythmia and hypertension during sevoflurane anaesthesia. However, further study is required to apply these findings to clinical anaesthesia.

Atrioventricular conduction during adenosine-induced hypotension in dogs anaesthetized with sevoflurane.

We have studied the effects of adenosine-induced hypotension on A-H interval (atrioventricular (AV) nodal conduction time during sinus rhythm), St-H interval (intra-atrial plus AV nodal conduction time during atrial pacing), H-V interval (His-Purkinje conduction time) and H-S interval (total ventricular conduction time) by His-bundle electrocardiography in addition to surface electrocardiogram during both sinus rhythm and atrial pacing in nine dogs anaesthetized with 1 MAC of sevoflurane. Stepwise increases in infusion rates of adenosine to 0.1, 0.3, 0.5 and 1.0 mg kg-1 min-1 produced a dose-related decrease in mean arterial pressure from 91 (6) to 38 (2) mm Hg. Adenosine significantly increased the A-H interval at infusion rates of 0.5 mg kg-1 min-1 and above, and the St-H interval at 1.0 mg kg-1 min-1. The H-V and H-S intervals remained unchanged. Heart rate decreased significantly only at 1.0 mg kg-1 min-1 with a significant increase in the PR interval. Adenosine-induced hypotension did not have deleterious effects on AV conduction times and the surface electrocardiogram in dogs anaesthetized with 1 MAC of sevoflurane. This may indicate that the effects of adenosine on AV conduction were small and therefore are unlikely to be a contraindication to the use of adenosine for inducing hypotension in patients with initially normal conduction during sevoflurane anaesthesia.

Hydroxymycotrienins A and B, new ansamycin group antibiotics.

New ansamycins designated hydroxymycotrienins A and B were isolated from culture broths of Bacillus sp. BMJ958-62F4. The two antibiotics inhibited more strongly the growth of human cervical cancer cell lines of human papilloma virus (HPV) positive than that of HPV negative cell lines. The structures, some biological and biochemical properties are reported.

Airway management for patients with a tracheal bronchus.

A tracheal bronchus is an aberrant, accessory or ectopic bronchus arising almost invariably from the right lateral wall of the trachea, causing hypoxaemia, atelectasis, or both, during anaesthesia. We describe two patients with a tracheal bronchus found before anaesthesia. One tracheal bronchus was found by tracheobronchoscopy and the other by chest x-ray. Because of recognition of the anomaly before operation, anaesthesia was uneventful in each patient.

[Anesthesia in a patient with history of multiple drug allergies].

A 38-year-old woman was admitted for intranasal ethmoidectomy. She had a history of serious anaphylactic reactions, including respiratory distress, hypotension and unconsciousness, to nonsteroidal anti-inflammatory drugs (Loxonin, Niflan) and antibiotics (Kefral, Minomycin). Preoperative intradermal skin tests against anesthesia-related drugs showed positive reactions to succinylcholine and vecuronium. After bilateral maxillary nerve block with 0.5 % bupivacaine (negative intradermal test) 3 ml, anesthesia was induced with diazepam, nitrous oxide, oxygen and sevoflurane. Trachea was intubated smoothly without muscle relaxants. Anesthesia was maintained with nitrous oxide, oxygen and sevoflurane 0.5-1 %. The anesthesia and postoperative course of this patient were uneventful. To confirm the initiation of allergic reaction to anesthetics used in the patient, serum histamine, tryptase, and complement 1, 3 and 4 factors were measured at 3 points: preoperatively, immediately after the induction, and after extubation. They showed normal levels. These results showed that no allergic reaction occurred perioperatively. In conclusion, the valuable information was provided for the choice of anesthetics by thorough evaluation of the past history and intradermal testing.

[Continuous epidural buprenorphine for postoperative pain relief after thoracotomy].

To evaluate postoperative analgesia and side effects of epidural buprenorphine, 60 patients after thoracotomy were divided into 6 groups. All patients received a bolus epidural administration of buprenorphine 0.1 mg in 8 ml of 0.25% bupivacaine. Following this epidural bolus, 10 patients in each group were given 0.25% bupivacaine alone (group A), buprenorphine 5 micrograms in 1 ml of 0.25% bupivacaine (group B), buprenorphine 8 micrograms in 1 ml of 0.25% bupivacaine (group C), buprenorphine 12 micrograms in 1 ml of 0.25% bupivacaine (group D), buprenorphine 15 micrograms in 1 ml of 0.25% bupivacaine (group E) or buprenorphine 18 micrograms in 1 ml of 0.25% bupivacaine (group F) with a portable disposable device at a rate of 1 ml.h-1 for 48 h. The percentages of patients who did not need additional narcotics for the first 24 hours postoperatively in group A, B, C, D, E, and F were 20%, 40%, 30%, 50%, 60%, and 70%, respectively. Those for the second 24 hours postoperatively in each group were 40%, 50%, 70%, 60%, 90%, and 90%, respectively. No significant difference in the incidence of side-effect was found among 6 groups. We concluded that optimal epidural doses of buprenorphine for post-thoracotomy pain relief are 15 and 18 micrograms.h-1 in the first and second 24 hours postoperatively, respectively.

[Meralgia paresthetica after spinal anesthesia].

A 27-year-old man underwent appendectomy under spinal anesthesia with 0.3% dibucaine 2.7 ml. The perioperative course was uneventful. The surgical procedure, however, lasted for 1.5 hours in the supine position. On the second postoperative day, a postspinal headache occurred and lasted for 18 days. On the seventh postoperative day the patient complained of numbness along the anterolateral aspect of the left thigh innervated by the lateral cutaneous nerve. There was no reflex or motor deficit indicative of the involvement of other nerves. The disorder was diagnosed as meralgia paresthetica caused by the surgical procedures. The numbness disappeared after the oral administration of mecobalamin in several days. In the treatment of a case like this, it is important to exclude neurological complications caused by spinal anesthesia.