Thoughts and Progress

In recent years, extracorporeal membrane oxygenation (ECMO) has been used for treatment of neonates with respiratory failure. A prototype of a compact ECMO system for neonates was developed. A single-lumen catheter, inserted into the right atrium via a jugular vein, was used for withdrawal and infusion of blood through the catheter. An extracapillary flow hollow-fiber membrane lung made of microporous polypropylene has a total surface area of 0.6 m2. To prevent the increase of plasma free hemoglobin, the ratio of withdrawal/infusion is controlled by a microcomputer. The system is compact in size with a low priming volume (less than 90 ml), which allows for ECMO with no additional blood transfusions. Its potential application as a respiratory support system is evaluated in animal experiments. The total intermittent veno-veno bypass flow was 15-30 ml/min/kg. The O2 transfer rate was 20 ml/min and the CO2 transfer rate was 33 ml/min at a blood flow rate of 300 ml/min. The O2 and CO2 exchange with the ECMO system was efficient enough to eliminate the respiratory failure induced by mechanical ventilation. The increase in plasma free hemoglobin was only 4 mg/dl after 6 h of ECMO. The system was considered applicable to respiratory aid for neonates.     

Noninvasive in vivo determination of intracerebral oxygen concentration in rats by a longitudinally detected ESR (LODESR) technique.

We have developed a noninvasive method to determine oxygen concentration in the brain tissue of rats in vivo. The method is based upon measuring the fundamental harmonic-to-secondary harmonic ratio (FSR) of longitudinal magnetization changes of a blood-brain barrier (BBB)-permeable nitroxide radical, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (hydroxymethyl-PROXYL), by employing a longitudinally detected ESR (LODESR) spectrometer operating at an ESR frequency of 280 MHz. FSRs of phantoms, including a hydroxymethyl-PROXYL solution and various concentrations of oxygen, were measured. We found that the FSRs of the phantom increased as the oxygen concentration increased. In vivo FSRs in the brains of rats that had received a hydroxymethyl-PROXYL injection were measured without the use of any surgical procedures. It was found that when the rats breathed 100% oxygen, rather than normal air, the FSR was significantly greater.     

Ethanol-induced vasoconstriction causes focal hepatocellular injury in the isolated perfused rat liver.

The role of microcirculation in the pathogenesis of alcoholic liver injury was investigated in isolated perfused livers from fed rats. Infusion of ethanol into the portal vein at concentrations ranging from 25 to 200 mmol/L increased portal pressure, which is an indicator of hepatic vasoconstriction, in a concentration-dependent fashion. Portal pressure started to rise immediately on initiation of ethanol load and remained at higher than basal levels throughout the period of ethanol infusion. Release of lactate dehydrogenase, an indicator of cell injury, into the effluent perfusate began to increase after 20 to 30 min of ethanol infusion and continued to increase until the end of the experiment (60 min after the initiation of ethanol infusion). The lactate dehydrogenase level in the effluent perfusate at 60 min was dependent on the ethanol concentration (0 mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 22 +/- 3 IU/L; 50 mmol/L, 51 +/- 11 IU/L; 100 mmol/L, 60 +/- 7 IU/L; 200 mmol/L, 120 +/- 7 IU/L). Simultaneous infusion of sodium nitroprusside (100 mumol/L), a known vasodilator, inhibited significantly the ethanol-induced increases in portal pressure and lactate dehydrogenase release by abolishing hepatic vasoconstriction. In histological examinations focal hepatocellular necrosis, evidenced by trypan blue staining of cell nuclei, was detected predominantly in midzonal and pericentral areas of the liver lobule after 60 min of ethanol infusion. Change in portal pressure during 60 min of ethanol infusion correlated significantly with levels of lactate dehydrogenase after ethanol infusion (r = 0.82; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Results of radiation therapy for squamous cell carcinoma of the uterine cervix using high dose-rate intracavitary irradiation]

We retrospectively analyzed 216 previously untreated patients with cervical cancer treated by high dose-rate intracavitary irradiation between 1978 and 1986. Cumulative 5-year survivals in stage Ib, IIa, IIb, IIIa, IIIb and IVa were 72.3%, 88.9%, 68.9%, 75.0%, 64.0% and 16.7%, respectively. Cause-specific 5-year survivals in stage Ib, IIa, IIb, IIIa, IIIb and IVa were 93.3%, 88.9%, 74.7%, 75.0%, 68.9%, and 18.8%, respectively. Recurrences outside the pelvis in stage IIb and IIIb (14.9% and 24.0%) were more common than loco-regional recurrences (10.3% and 12.0%). However, loco-regional recurrences (50%) were most frequent in stage IVa. Thirteen patients (6.0%) required surgical management for intestinal complications (severe). Six patients (2.7%) died due to intestinal complications (fatal). These fatal and severe complications were closely correlated with the dose of external radiation. These data suggest that intracavitary irradiation using a high dose-rate system is useful for the treatment of uterine cancer; however, further efforts to reduce intestinal complications by lowering the dose of external radiation will be necessary. It is also suggested that a combined modality, such as chemotherapy, is necessary for controlling metastases outside the pelvis in stage IIb and IIIb, and for local control in stage IVa.     

Medulloblastoma in the first year of life: A report of five cases

Five infants with cerebellar medulloblastoma, who all presented within the first year of life, are presented. The initial characteristic presenting symptoms included vomiting and macrocrania, frequently followed by a delay in normal development. No patients showed any signs or symptoms of cerebellar dysfunction. One infant, who was initially diagnosed as having a congenital hydrocephalus, died 4 months after undergoing a cerebrospinal fluid shunt operation, while the remaining four patients all underwent direct surgery for their tumors and three also received an additional course of postoperative radiation therapy. Of these four patients, three died within 4 years after diagnosis, with a mean survival period of 2.7 years, whereas one is still alive after a follow-up period of more than 20 years. However, the patient does suffer from both physical and intellectual handicaps. The clinical and histological features of infantile medulloblastomas are reviewed while the therapeutic problems associated with these tumors are also discussed.     

Capillary blood flow and arteriolovenular shunt in various organs in hypotensive states induced by nitroglycerine,nitroprusside, and nicardipine

The capillary blood flow of 14 organs was measured in dogs using the microsphere (9μm diameter) trapping method under hypotension induced by administration of either nitroglycerin (NTG), nitroprusside (SNP), or nicardipine (NIC). Simultaneously, blood flow through the arteriolovenular shunt in the brain, kidney, liver, mesenteric organs, skeletal muscles of the pelvic limb, and all organs in the body, except the lungs, were measured by collecting venous blood drained from the organs at 4.8 ml·min⁻¹ for 2 min. Capillary blood flow remained unchanged in most organs under hypotension with either NTG or SNP, but in increased in most organs, together with an increase in cardiac output, under hypotension with NIC. Arteriolovenular shunt tended to increase in four organs, with the exception of the liver, and increased in the whole body under hypotension with NTG. However, arteriolovenular shunt remained unchanged under hypotension with SNP. Arteriolovenular shunt increased in the mesenteric organs under hypotension with NIC, but decreased in the skeletal muscles of the pelvic limb. These results indicated that none of these hypotensive drugs impairs the nutrient supply to organs; further, NIC protects it much more since it does not increase the shunt flow through major organs.