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Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation.

To determine whether there are significant alterations in cerebral blood flow patterns in infants with a patent ductus arteriosus and whether these alterations correlate with alterations in aortic blood flow, we performed range-gated pulsed-Doppler examinations of the aorta and cerebral arteries in 20 infants. Ten infants had a PDA and ten control infants did not. We analyzed these flow patterns quantitatively by calculating the pulsatility index (peak systolic frequency minus trough diastolic frequency)/peak systolic frequency. In the ten control infants and in three infants with a small PDA, there was no significant diastolic flow in the descending aorta; flow in the cerebral arteries was antegrade throughout systole and diastole (PI = 0.75 +/- 0.03 for control infants and 0.73 +/- 0.07 for small PDA infants). In seven infants with a large PDA, there was retrograde diastolic flow in the descending aorta. This pattern was not seen after PDA closure. In the cerebral arteries of the seven infants with a large PDA, diastolic flow was retrograde in three and decreased or absent in four, and PI was significantly higher (PI = 0.96 +/- 0.06. P less than 0.001 vs controls). After PDA closure, cerebral diastolic flow was antegrade in all seven infants (PI = 0.74 +/- 0.04). We conclude that a large PDA can cause abnormal flow patterns in the descending aorta and cerebral arteries. These flow patterns may predispose these infants to CNS ischemia or intraventricular hemorrhage.

Tyramine permeates chromaffin-granule membranes via a reserpine-insensitive mechanism. The rate is unsaturable and increases with pH, indicating permeation of the unprotonated form of the amine. Reserpine-insensitive dopamine uptake is at least 10 times slower, consistent with dopamine's lesser lipophilicity. Dopamine is transported into chromaffin-granule membrane vesicles via a saturable, reserpine-sensitive, proton-linked mechanism. Tyramine inhibits dopamine transport with a Ki of 5-10 microM. Tyramine is not accumulated nearly as well as dopamine because inward transport is opposed by outward permeation. Nevertheless, the velocity of reserpine-sensitive tyramine transport can be deduced from the steady-state level of tyramine accumulation and the rate of permeation. Vmax for tyramine transport is about one-third of the value for dopamine transport. Therefore, two aromatic hydroxyls are not needed for monoamine transport but are required for efficient accumulation and storage.

The evaluation of pharmacologic effects in perinatal medicine is dependent on our clinical methods for measurement and monitoring of the mother, the fetus, and the newborn infant. The development of a noninvasive continuous method of measuring PO2, the transcutaneous PO2 electrode, has greatly enhanced the ability to assess effects of drugs on the cardiorespiratory system. During labor, diazepam and meperidine have been documented to cause respiratory depression and significant decreases in PO2. The advantageous effect of epidural anesthesia on the oxygen-cardiorespirogram of mothers in labor has also been demonstrated. Both fetal and maternal tcPO2 have been successfully assessed during the administration of peridural catheter anesthesia (carticaine) and during suppression of labor with fenoterol. In the newborn infant, monitoring of tcPO2 has been helpful in assessing the residual effects of drugs administered during labor and delivery, in prescribing the appropriate and safe dose of oxygen, and in defining the effects of theophylline on the oxygen-cardiorespirogram. We have also demonstrated the effect of furosemide on PO2 in the treatment of pulmonary edema accompanying bronchopulmonary dysplasia and of indomethacin for the management of patent ductus arteriosus. Use of tcPO2 measurements for clinical pharmacologic evaluation is a promising addition to our research techniques.

The authors review the function, reliability, risks, and clinical applications of skin surface blood gas monitoring that have become evident during the first decade of its clinical use. Also discussed is the problem of data expression and the recent developments in this area.

Recent advances have made organ transplantation in newborns feasible, but the paucity of organs small enough for this age group remains a major limitation. Because anencephalic infants can survive for no more than a few weeks, they have been considered as possible organ donors for other infants. Under current law, however, they cannot be used as donors until their brain-stem activity ceases and the criteria for total brain death are thereby met. If anencephalic infants receive customary care, their solid organs usually undergo irreversible hypoxic injury during the process of dying and become unsuitable for donation by the time of death. We modified the medical care of 12 live-born anencephalic infants for one week to determine whether organ viability could be maintained and whether the criteria of total brain death could be met. Six received intensive care from birth, and six only when signs of imminent death developed. Only two infants met the criteria for total brain death within one week, and no solid organs were procured. Most organs were suitable for transplantation at birth. When intensive care was provided from birth, organ function was maintained; however, brain-stem activity ceased in only one infant within the first week. When intensive care was delayed until death was imminent, most organs were damaged to an extent that made them no longer suitable for transplantation. Our findings suggest that it is usually not feasible, with the restrictions of current law, to procure solid organs for transplantation from anencephalic infants.

Thirty-three patients over a 21-year period underwent thoracotomy for resection of suspected pulmonary metastases from malignant melanoma. Eleven patients were found to have nonmalignant disease (Group 1); 10 were found to have unresectable disease (Group 2); and 12 were rendered disease-free (Group 3). Of the patients found to have melanoma, 20 of 22 received post-operative chemotherapy. The median survival of the patients in Group 2 was 10.5 months (3 to 20 months); in Group 3 it was 12 months (3 to 35 months). There were no 5-year survivors. No factors distinguished the three groups preoperatively. Surgical resection still offers the greatest chance for long-term survival, based on reports of patients in the literature who have survived longer than 5 years following resection of pulmonary metastases from melanoma. Thoracotomy is especially useful for staging purposes in those patients found to have no metastatic disease.

We studied the effects of six different head positions on intracranial pressure and cerebral blood flow velocity in six infants with a recent history of asphyxia and eight without. ICP was measured noninvasively using a transfontanel pressure transducer, and CBF was assessed using the continuous-wave Doppler method. We found that ICP was lowest with the head elevated and in the midline (P less than 0.01), and that ICP was higher in all infants in the dependent position (P less than 0.001). This increase was significantly greater in those who had had an episode of asphyxia during the 48 to 72 hours prior to the study (P less than 0.02). Therefore, we recommend a head elevation of 30 degrees in the midline in any infant with increased ICP or at high risk for cerebral injury, and caution against the use of the dependent position in these infants.

A series of 31 patients treated for ruptures and perforations of the intrathoracic esophagus is reviewed. Eighteen of these patients underwent major thoracotomy; 11 were treated with minor procedures. Two died before treatment could be implemented. Of the 18 undergoing major operations, 7 died; among the 11 managed conservatively there was only 1 death. Based on this experience, we conclude that major surgical repair for esophageal perforation is often unnecessary. It has the additional drawback of sometimes resulting in equally serious secondary procedures.

Continuous monitoring of oxygenation in sick newborns is vitally important. However, transcutaneous PO2 measurements have a number of limitations. Therefore, we report the use of the pulse oximeter for arterial oxygen saturation (SaO2) determination in 26 infants (birth weights 725 to 4,000 g, gestational ages 24 to 40 weeks, and postnatal ages one to 49 days). Fetal hemoglobin determinations were made on all infants and were repeated following transfusion. SaO2 readings from the pulse oximeter were compared with the SaO2 measured in vitro on simultaneously obtained arterial blood samples. The linear regression equation for 177 paired measurements was: y = 0.7x + 27.2; r = .9. However, the differences between measured SaO2 and the pulse oximeter SaO2 were significantly greater in samples with greater than 50% fetal hemoglobin when compared with samples with less than 25% fetal hemoglobin (P less than .001). The pulse oximeter was easy to use, recorded trends in oxygenation instantaneously, and was not associated with skin injury. We conclude that pulse oximetry is a reliable technique for the continuous, noninvasive monitoring of oxygenation in newborn infants.

A national conference on Medical Education in China for the 21st Century was convened in Beijing in November 1986. Over 6 days, leading medical educators and Ministry of Public Health officials from across China presented China's future health service needs and debated opportunities and constraints in meeting those needs by various innovations in medical education. Recent political upheavals have left many educators wary of innovation. There are major, conflicting demands between the needs of rural primary care service and the needs of medical schools to replenish medical school professional ranks depleted by the Cultural Revolution. Multiple and varied experiments in medical education will be encouraged among China's medical schools. China will probably amalgamate indigenous and foreign education experiments, offering the world community new and important innovations in medical education.

Transcutaneous PO2 (tcPO2) monitoring offers a new approach to the evaluation of drug effects. We investigated the effect of theophylline on ten premature infants with apnea. Theophylline was administered as aminophylline, 8 mg/kg per rectum every 12 hours for two doses and 4 mg/kg every 12 hours for a total of two or five days (short and long courses). The tcPO2, heart rate (beat-to-beat), and thoracic impedance were continuously monitored during each of three 4-hour study periods: 12 hours before theophylline administration, 12 hours after initiation of theophylline therapy, and 24 to 48 hours after discontinuing the drug's use. Plasma levels were measured by a radioimmunoassay developed in our laboratory. Polygraphic recordings were analyzed without knowledge of treatment for frequency of apneic spells, mean duration of apneas, total duration of hypoxemia (tcPO2 less than or equal to 40 torr), total duration of hyperoxemia (tcPO2 greater than or equal to 100 torr), basal tcPO2, heart rate, and respiratory rate. In each case during theophylline use, cardiorespiratory patterns were altered, respirations were more regular, apneic spells were reduced, PO2 was stabilized with less hypoxia and hyperoxia, and bradycardic episodes were decreased. There was considerable variation in the response of the ten infants and a significant difference in the frequency of return of symptoms between those receiving short-term therapy and those receiving the longer course.

In summary, our findings support and confirm the concerns of many investigators that present methods of cardiorespiratory monitoring are inadequate for the detection of many forms of apnea. Nurses underrecord both the frequency and duration of apneic episodes. Bradycardia is an unreliable index of hypoxemia. Thoracic impedance monitors are unreliable because they detect only a fixed duration of respiratory pause and are sensitive to many artifacts unavoidable in a clinical setting. Finally, ineffective breathing patterns such as disorganized breathing, obstructive apnea, and paradoxical breathing are undetectable by thoracic impedance monitoring. We warn against the reliance on heart rate and thoracic impedance monitoring alone for infants with recurrent apnea.

A case of primary adenoid cystic carcinoma of the esophagus is reported and a total of 15 cases was reviewed. There were 9 men, although earlier reports indicated the disease was more common in women. The lesion was located in the middle third of the esophagus in 10 cases. The possibility of tumor development from embryonal rests of the tracheobronchial tree in the esophagus is discussed. The prognosis of adenoid cystic carcinomas is not well known, but the treatment and prognosis appear similar to those of epidermoid carcinomas of the esophagus.

The clinical usefulness of the transcutaneous O2 electrode was investigated in 30 sick infants; 159 simultaneous measurements of arterial PO2 and transcutaneous PO2 were made. During the comparisons, arterial blood pressure, heart rate, and thoracic impedance were continuously recorded, and skin axillary and environmental temperatures and hematocrit were noted. Despite a wide range of arterial blood pressure and hematocrits, arterial PO2 and transcutaneous PO2 were similar (slope, 0.963), except for 2 groups of sick infants. Some infants with severe, persistent pulmonary hypertension who were receiving an intravascular infusion of tolazoline and infants with mean arterial blood pressures more than 2.5 SD less than the predicted average had values for transcutaneous PO2 that were lower than PO2. The surface O2 electrode is safe and relatively easy to use and provides data that can help in the management of most sick infants.

We investigated the characteristics of non-aqueous solvents for tcPO2 electrolytes, using a tcPO2 electrode with three 15 micrometer platinum cathodes set in a polished glass surface, a 17.8 mm2 silver anode covered with a 25 micrometer Telfon membrane, with and without a 12 micrometer cellophane spacer, and polarized at--0.8v. We examined the effect of ethylene glycol (EG) concentration, in water, on O2 sensitivity, stirring effect, in vitro drift, in vitro response time, behaviour on the skin of newborn infants and in vivo response time. We found the following: (1) O2 sensitivity was reduced by increasing EG concentration. (2) phi, the stirring effect (gas/50% glycerine) was 1.01 at 90% EG with cellophane, but higher without cellophane. (3) In vitro drift at 44 degree C electrode temperature, in 43 degree C water (simulating skin), was reduced with 90% EG, 25 micrometer Telfon and no spacer, but increased with a spacer. (4) In vitro response time was increased with EG. (5) Correlations with arterial PO2 in a group of newborns was as excellent with an electrode made with 90% EG and 25 micrometer Telfon, without spacer, as it was with our previous study using aqueous electrolyte and 12 micrometer Telfon wint 12 micrometer cellophane: (tcPO2 = 1.32 + 0.988 PaO2 r = 0.987). In vivo response time was not prolonged. Using EG, the tc PO2 electrode membrane required changing only after 7--9 days, compared with 1--2 days when using aqueous electrolytes. No advantage of using cellophane spacers was identified in these in vivo studies.

In summary, the pulse oximeter provides a reliable, continuous assessment of oxygenation in newborn infants. Its rapid response time and ease of use make it a practical device for use on all sick newborns. To avoid hyperoxia it should be used in conjunction with arterial blood gas measurements and we recommend a high SaO2 alarm of 92% in infants with predominantly fetal hemoglobin. Finally, it is an improved way of monitoring oxygenation in very immature infants and in infants with bronchopulmonary dysplasia.

Patients with fibrosing mediastinitis causing obstruction of pulmonary veins and arteries may present with many of the historic, physical, and laboratory findings of patients with pulmonary hypertension due to chronic thrombotic obstruction of major pulmonary arteries. Because the latter is subject to surgical correction, and the former is not, it is important to differentiate between the two and to be aware of the similarities in presentation. Three patients with pulmonary hypertension due to compression of pulmonary veins and the right pulmonary artery by fibrosing mediastinitis are presented who illustrate these points. A review of the literature documents other instances in which vascular involvement due to fibrosing mediastinitis has mimicked other types of pulmonary hypertension.

Review of the world literature to the end of 1971 has provided data on 838 cases of esophageal leiomyomata, including our own 19 surgically removed lesions. Although esophageal leiomyoma is the most common of the benign tumors of the esophagus, it is still rare compared with carcinoma. It occurs in more men than women, by a ratio of 1.9 to 1. Over 50% of the patients with leiomyoma of the esophagus are asymptomatic. Dysphagia and vague pain are the most frequent symptoms. Pyrosis is mentioned in the literature as present in 40% of the cases, but it is considered mainly as symptom of coexistent hiatal hernia. Diagnostic problems often arise, as the smooth muscle tumors may mimic mediastinal neoplasms, cysts, or even aneurysms, or complicate coexisting hiatal hernia and esophageal diverticulum. Operative management by transthoracic enucleation is the procedure of choice, although resection of the esophagaus may be required in few cases. Postoperative morbidity is minimal and results are excellent.

We investigated the clinical use and limitations of the transcutaneous oxygen electrode described by Huch, Lübbers and Huch in 30 sick infants. One hundred and fifty-nine measurements of arterial oxygen tension (PaO2) and transcutaneous oxygen tension (tcPO2) were made. During the comparisons, arterial blood pressures, heart rate thoracic impedance were continuously recorded, skin axillary and environmental temperatures, hematocrit and skin thickness were measureed and the degree of peripheral perfusion noted. Despite a wide range of these variables, values of tcPO2 and PaO2 were similar (slope 0.963). Two groups of infants were identified in whom tcPO2 was lower than PaO2. These were infants receiving an intravascular infusion of tolazoline and infants with mean arterial blood pressures more than 2.5 s.d. below the predicted average value. Both of these situations represent extreme alterations in peripheral blood flow and give important information regarding the limitations of the method. Less extreme alterations in flow caused by mild hypotension, hypothermia, anemia, radiant warmers, and bilirubin lights did not adversely affect the transcutaneous PO2--arterial PO2 correlation. Advantages of transcutaneous oxygen monitoring over more conventional monitoring methods were assessed. We conclude that the transcutaneous oxygen electrode is safe, is easy to use, has few limitations and provides data which can help improve the management of most sick infants.