Bronchial atresia with relapsing pulmonary infection in a middle-aged man.

Congenital bronchial atresia (CBA) is a rare disorder, first reported in 1953. Less than 100 cases are reported in the literature, mostly in young, asymptomatic male patients with involvement of the apical-posterior segment of the left upper lobe. Patients may complain of fever, cough, or shortness of breath, symptoms that result from post-obstructive, sometimes recurrent, infections. Chest radiography and computed tomography reveal a tubular branching density representing mucus impaction or mucocele with surrounding focal hyperinflation. Surgical excision is reserved for symptomatic cases. We report an unusual case of CBA in a middle-aged man with a history of relapsing infections, who was found to have an atretic superior segment of the left lower lobe, with surrounding areas of organizing pneumonia.

Control of fetal insulin secretion.

In this study, we investigated the way in which fetal insulin secretion is influenced by interrelated changes in blood glucose and sympathoadrenal activity. Experiments were conducted in late gestation sheep fetuses prepared with chronic peripheral and adrenal catheters. The fetus mounted a brisk insulin response to hyperglycemia but with only a minimal change in the glucose-to-insulin ratio, indicating a tight coupling between insulin secretion and plasma glucose. In well-oxygenated fetuses, alpha(2)-adrenergic blockade by idazoxan effected no change in fetal insulin concentration, indicating the absence of a resting sympathetic inhibitory tone for insulin secretion. With hypoxia, fetal norepinephrine (NE) and epinephrine secretion and plasma NE increased markedly; fetal insulin secretion decreased strikingly with the degree of change related to extant plasma glucose concentration. Idazoxan blocked this effect showing the hypoxic inhibition of insulin secretion to be mediated by a specific alpha(2)-adrenergic mechanism. alpha(2)-Blockade in the presence of sympathetic activation secondary to hypoxic stress also revealed the presence of a potent beta-adrenergic stimulatory effect for insulin secretion. However, based on an analysis of data at the completion of the study, this beta-stimulatory mechanism was seen to be absent in all six fetuses that had been subjected to a prior experimentally induced hypoxic stress but in only one of nine fetuses not subjected to this perturbation. We speculate that severe hypoxic stress in the fetus may, at least in the short term, have a residual effect in suppressing the beta-adrenergic stimulatory mechanism for insulin secretion.

The utility of sestamibi scanning in the operative management of patients with primary hyperparathyroidism.

BACKGROUND: The role of imaging studies before parathyroidectomy has been extensively debated and recent advances in unilateral parathyroidectomy intensify this controversy. The purpose of this study was to review the parathyroidectomy experience of a single surgeon, looking at the role of sestamibi scans and a standard postoperative care regimen. STUDY DESIGN: Retrospective review of office and hospital charts was completed on 90 patients with primary hyperparathyroidism who underwent parathyroidectomy from 1991 to 1998. Patient workup and outcomes were noted, as were results of preoperative imaging. True-positive scans visualized an abnormality ipsilateral to the adenoma found at operation. Statistics were performed using nonparametric testing and Student's t-test. RESULTS: There were 21 male and 69 female patients, with an average age of 54 years (range 29 to 81). There were zero mortalities, three morbidities (3.3%), and three patients who had persistent hypercalcemia, yielding a 96.7% success rate. Sixty-seven patients underwent preoperative sestamibi scanning, with a sensitivity of 74% and positive predictive value of 89%. Operative time in imaged patients averaged 103 +/- 49.9 minutes versus 121.5 +/- 85.9 minutes for patients without sestamibi scans. Operating time differences were not statistically significant and a preoperative sestamibi scan did not affect the success of parathyroidectomy. Discharge on postoperative day 1 was accomplished in 80% of patients and 13% were discharged the next day. There was no morbidity from hypocalcemia. CONCLUSIONS: A preoperative sestamibi scan does not improve efficacy or decrease operating time for primary hyperparathyroidism when bilateral neck exploration is performed. A postoperative care protocol including oral calcium and vitamin D supplementation allows the majority of patients to be discharged on postoperative day 1 with excellent results.

Analysis of cell type and radiographic presentation as predictors of the clinical course of patients with bronchioalveolar cell carcinoma.

STUDY OBJECTIVES: Bronchioloalveolar carcinoma is a primary lung neoplasm of variable histopathologic, radiologic, and clinical expression. There are three cell types described in bronchioloalveolar carcinoma: Clara cells, mucin-producing cells, and alveolar type II epithelial cells. It is unclear whether these three tumor cell types are associated with a specific radiologic presentation and clinical course. In this study, we investigated whether tumor cell type, identified by transmission electron microscopy, correlated with a specific radiologic pattern, and whether tumor cell type or radiologic presentation correlated with the patient's clinical course and outcome. DESIGN: Transmission electron microscopy was used to restudy tissue blocks from the original surgical histopathologic specimens in 54 patients with primary bronchioloalveolar carcinoma diagnosed over a 10-year period (1980 to 1990). The pretreatment radiographs were reviewed in each case, and the first chest radiograph obtained at the time of the discovery of the tumor in each patient was compared with the results of the ultrastructural study. The medical records of each patient were examined to obtain pertinent radiologic, clinical, and patient outcome information. MEASUREMENT AND RESULTS: There were 32 Clara cell tumors, 10 mucin-producing cell tumors, and 1 alveolar type II epithelial cell tumor in this series. Eleven additional tumors had mixtures of two or more cell types. No statistically significant relationship was detected between tumor cell type and radiologic presentation or patient mortality pattern. There was increased mortality among patients who presented radiologically with segmental, lobar, multifocal, or diffuse disease compared with those patients exhibiting a solitary pulmonary nodule at presentation. CONCLUSION: Radiologic presentation, rather than tumor cell type, provides prognostic information that aids in predicting patient outcome.

Sonographic guidance for the localization of peripheral pulmonary nodules during thoracoscopy.

OBJECTIVE: The value of sonographic guidance during video-assisted thoracoscopic surgery (VATS) was studied in 13 patients with one or more peripheral pulmonary nodules who later underwent wedge resection. SUBJECTS AND METHODS: After a review of the chest radiographs and CT scans of each patient, sonographic guidance for VATS was requested by the attending surgeon when the nodule or nodules in question were determined to be too small or too deep in the lung parenchyma from the pleural surface for location by VATS. A multifrequency (5.0-, 6.5-, or 7.5-MHz) sonographic probe was introduced through a thoracoscopic port during VATS. The nodule or nodules in question were located by intraoperative sonography or determined by inspection and confirmed by sonography before wedge resection. The size and location of each lesion and the time needed for sonographic guidance were recorded. RESULTS: Sonography revealed a peripheral pulmonary nodule in 12 of the 13 patients. Of these, it confirmed the suspected location of the pulmonary nodule in six. In the remaining six patients, the surgeon was unable to locate the nodule without the use of sonography. The additional operative time required for sonographic guidance during VATS averaged 7.5 min. However, the time commitment of radiology personnel during surgery varied and was sometimes lengthy (maximum, 150 min). CONCLUSION: Sonographic guidance during thoracoscopy helped to locate lesions and determine their size and proximity to pleural surfaces. Sonographic guidance can be done safely and can be completed expeditiously. Unlike percutaneous hookwire techniques, sonographic guidance does not require an additional invasive procedure to locate the peripheral pulmonary nodule.

The adrenal secretion of catecholamines during systemic metabolic acidosis in fetal sheep.

This study was undertaken to determine whether or not metabolic acidemia per se stimulates catecholamine (CA) secretion from the adrenal medulla in fetal sheep. The potential confounding effect of low O2 content, occasioned by the right shift in the oxyhemoglobin dissociation curve with acidemia, was taken into account in experimental design. Hemodynamic values, blood gases, O2 content, lactate and glucose concentrations and adrenal CA secretion rates and plasma CA levels were studied in fetal sheep at baseline and during control (saline infusion) and acidemic (15 and 30% lactic acid infusion) periods. Experiments were conducted after recovery from preparative operations performed under general anesthesia. Arterial pH did not change with saline infusion. During 15 and 30% lactic acid infusions, pH fell to 7.23 and 7.09, respectively, as lactate concentrations increased 4.7 and 10 times. Arterial PCO2 increased from 50 to 58 torr during 30% lactic acid infusion. Fetal CA secretion and plasma concentrations did not change during saline, or 15 or 30% lactic acid infusions. Moreover, hemodynamic parameters did not indicate increased CA secretion. In conclusion, we found no evidence for stimulation of adrenal CA secretion by metabolic acidosis.

Role of thoracoscopy and preoperative localization procedures in the diagnosis and management of pulmonary pathology.

Video-assisted thoracic surgery is an important component of modern thoracic surgery, providing a safe, less invasive alternative to open thoracotomy in the evaluation of pleural, mediastinal, and parenchymal pathology. Advancements in endoscopic techniques and video-optics have permitted greater visualization of the thoracic cavity and allowed limited pulmonary resections with significantly reduced postoperative morbidity. Thoracoscopy is indicated for diagnosis of intrathoracic pathology when usual methods of diagnosis, including fine-needle aspiration and transbronchial biopsy, are inconclusive. The diagnostic accuracy of video-assisted thoracic surgery approaches 100%. Increasingly, the indications for thoracoscopy include therapeutic resections of pulmonary nodules in cases of limited lung metastases and bronchogenic carcinoma when pulmonary function is poor. Successful diagnostic and therapeutic resection by thoracoscopy requires intraoperative localization of the lesion within the collapsed lung. The indications and methods of thoracoscopic surgery and preoperative localization are discussed.

Surgical treatment of secondary hyperparathyroidism in patients with chronic renal failure by sub-total parathyroidectomy.

The majority of patients with secondary hyperparathyroidism caused by chronic renal insufficiency are successfully managed medically. However, approximately 5-10 per cent develop refractory symptoms such as bone pain and pruritus requiring palliative surgical treatment. We present a series of 16 consecutive patients who were managed with sub-total parathyroidectomy over a 6-year period. With follow-up of 12-60 months, there were no operative mortalities or significant perioperative morbidities. All patients had significant improvement or resolution of their symptoms. All had biochemical improvement with reductions in their serum calcium and parathormone levels. No patients have required re-exploration for persistent or recurrent hyperparathyroidism, and there have been no cases of permanent hypoparathyroidism. We feel that sub-total parathyroidectomy remains the optimal treatment for refractory secondary hyperparathyroidism. It offers several advantages over total parathyroidectomy with autotransplantation.

Perioperative implantation of iridium-192 as the boost technique for stage I and II breast cancer: results of a 10-year study of 655 patients.

PURPOSE: To assess the efficacy of perioperative implantation of iridium-192 for stage I and II breast cancer. MATERIALS AND METHODS: The authors retrospectively reviewed findings from 655 patients with stage I and II cancer treated with conservative surgery and Ir-192 implantation between 1982 and 1992. Hollow plastic tubes were placed in the tumor bed as a single- or double-plane implant at lumpectomy. Ribbons with Ir-192 seeds were inserted into the tubes 4-6 hours later. The Ir-192 was left in place for approximately 50 hours. External-beam irradiation was given to the whole breast 10-14 days later. RESULTS: Follow-up ranged from 2 to 146 months. The local control at 10 years for stage I and II disease was 93% and 87%, respectively. The 10-year actuarial survival rate was 92% +/- 1 for stage I disease and 72% +/- 4 for stage II disease. The rate of survival with no evidence of disease for stage I and II disease combined was 82% +/- 1 at 5 years and 75% +/- 3 at 10 years. CONCLUSION: Perioperative implantation produced excellent local control equal to that with electron-beam therapy.

Hypoxia-induced sympathetic inhibition of the fetal plasma insulin response to hyperglycemia.

Large-for-delivery date babies, considered characteristic of diabetic pregnancy, are believed to result from fetal hyperinsulinemia. Paradoxically, infant birth weights tend to be low-for-delivery date in mothers with more severe diabetes. We tested the hypothesis that hypoxemia in such fetuses leads to sympathoadrenal stimulation and inhibition of insulin secretion; and, thus, produces a net reduction in the growth-promoting effects. Fetal sheep were prepared with chronic peripheral and adrenal cannulas. Fetal blood gases, lactate, norepinephrine, and epinephrine secretion rates; and plasma norepinephrine, glucose, and immunoreactive insulin concentrations were determined at 30-min intervals during a 2-h baseline period and a 4-h period of hyperglycemia divided into 2-h segments of hypoxemia (with and without alpha-blockade) and hyperoxia. Hypoxemia-hyperoxia sequences were varied randomly. Well-oxygenated fetuses responded to a threefold increase in glucose with a sixfold increase in plasma immunoreactive insulin. With hypoxemia, norepinephrine and epinephrine secretion were elevated and the insulin response was blocked. With hypoxemia and phentolamine blockade, the insulin response was enhanced with a 10-fold increase above baseline. In severe maternal diabetes with vascular disease or with poor control and very high glucose levels, the fetus is likely to be relatively hypoxemic. Our experiments suggest that in this situation, the fetal insulin response to hyperglycemia will be attenuated; this effect is mediated, at least partly, through sympathoadrenal stimulation.

Localization of peripheral pulmonary nodules for thoracoscopic excision: value of CT-guided wire placement.

OBJECTIVE: One of the indications for the rapidly expanding use of thoracoscopic surgery as an alternative to thoracotomy is the excision of peripheral lung nodules. Nodules judged too small or too far from the pleural surface to be seen or palpated during thoracoscopy must be localized beforehand. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous placement of spring hookwires to localize such nodules before video-assisted thoracoscopy. SUBJECTS AND METHODS: Under CT guidance, 17 nodules in 14 patients were preoperatively localized with the Kopans breast lesion localization system. Three patients who had solitary nodules had thoracoscopic resections for diagnosis because a previous transthoracic needle or transbronchial biopsy had been unsuccessful. Four patients who had lesions less than 8 mm in diameter had thoracoscopic biopsies because transthoracic fine-needle aspiration biopsy was not likely to be diagnostic. Seven patients, who had a total of 10 nodules, had therapeutic wedge resections of either limited metastases or a second bronchogenic carcinoma. Mean nodule diameter was 10 mm (range, 3-20 mm). The mean distance from nodule to costal pleura was 9 mm (range, 0-25 mm). At the end of the procedure, wire placement was confirmed by CT scanning. After thoracoscopy, the surgeons were questioned about the stability and utility of each hookwire localization. RESULTS: In all 17 procedures, a hookwire was placed successfully. In one case, the wire dislodged before thoracoscopy (after a 6-hr preoperative delay and severe bending of the wire during induction of anesthesia). In 16 of the 17 resections, the surgeon thought that thoracoscopic identification of the lesion would not have been possible without hookwire localization. Only one localization, across a major fissure, required placement of a second wire to localize a nodule. Wire-related complications included two instances of serious pain, five cases of clinically insignificant pneumothorax, and one large pneumothorax requiring drainage before a second nodule in the same lung was localized. CT scanning showed presumed local pulmonary hemorrhage in six cases without hemoptysis or hemothorax. CONCLUSION: CT-guided hookwire localization is easily and safely performed and permits thoracoscopic resection of lung nodules, which might otherwise be impossible.

Cause and current management of reoperative hyperparathyroidism.

We reviewed 137 cases of hyperparathyroidism followed for 6-72 months to determine the reasons for failure and to outline the successful management of reoperative hyperparathyroidism. Of 127 patients treated initially at Thomas Jefferson University Hospital, three required reoperation (2.4%) and 10 were referred with recurrent or persistent hyperparathyroidism. Reasons for failure were a missed gland in eight cases (62%), an ectopic gland in two cases (15%), supernumerary glands in two cases (15%), and malignant degeneration of an autotransplant in one case (8%). One patient had shortterm hypoparathyroidism requiring vitamin D supplementation (5.6%), but there were no injuries to the recurrent laryngeal nerves. We conclude that adequate knowledge of the location of normal and ectopic glands with meticulous search will reduce most reoperations, and, with identification of all four glands and routine cervical thymectomy in multigland disease, the rate should be less than 5 per cent. Patients requiring reoperation should undergo noninvasive localization studies and, if equivocal, selective venous sampling for parathyroid hormone. The major complication rate should be less than 10 per cent.

Sonographically guided laparoscopy and mediastinoscopy using miniature catheter-based transducers.

Miniature ultrasound transducers (12.5 MHz) housed in 9 Fr catheters were passed through a laparoscope or mediastinoscope to image a variety of normal and abnormal structures within the peritoneal cavity and mediastinum in 20 patients. These transducers made it possible to visualize the gallbladder and bile ducts and evaluate for the presence of stones, to detect masses and provide guidance for their aspiration or biopsy, and to image the internal structures of the ovary and fallopian tube. In addition, these miniature transducers were used to locate such normal vital structures as blood vessels, thereby allowing the surgeon to decide on the best approach for dissection during mediastinoscopy. During conventional surgery, the surgeon or gynecologist can palpate an area of abnormality not directly visualized. However, during laparoscopy and mediastinoscopy direct palpation is not possible. Therefore, it is important to find another method to determine what structures lie beneath the visualized surface. These miniature ultrasound transducers appear to offer a means for making such determinations.

Adrenal corticosteroid secretion in fetal sheep: pulsatile pattern at rest.

This study was undertaken to define the resting pattern of fetal pituitary-adrenocortical function. Experiments were performed at 127-145 days gestation in fetal sheep with chronic peripheral and adrenal cannulas inserted under halothane anesthesia. With the fetus in a baseline state, over 6 h, at 30-min intervals, maternal and fetal peripheral samples were collected for blood gases and cortisol (F), corticosterone (B), and adrenocorticotropic hormone (ACTH) concentrations, and three successive, 2-min adrenal samples were collected for determination of F and B secretion rates. We observed high-frequency, episodic bursts of F secretion. A lower frequency oscillation of F secretion, with a period of approximately 90 min, was defined by cosinor analysis. The mean amplitude of the oscillation increased from 45 to 507 ng/min with advancing gestation. The pattern of B secretion was similar to that for F but was quantitatively lower. An oscillatory period of approximately 90 min for plasma F was present in a majority of experiments. Pulsatile rhythms for ACTH were defined in 10 of 14 experiments, with periods ranging from 1.64 h in the least mature group to 2.37 h in the oldest fetus. Mean data revealed exponential increases in both F secretion and plasma ACTH from 129 to 145 days gestation.

The effect of hyperglycemia on acid-base and sympathoadrenal responses in the hypoxemic fetal monkey.

We investigated the influence of hyperglycemia on the fetal acid-base and sympathoadrenal responses to hypoxemia (maternal FIO2 9%) in rhesus monkey fetuses. In chronic preparations, we determined PO2, O2 content, PCO2, pH, lactate, glucose, insulin, catecholamines, heart rate, and arterial pressure. Combined hyperglycemia and hypoxemia resulted in a decrease in fetal pH and an increase in lactate; however, the magnitude of these changes was only modestly, and not significantly, greater than those observed during euglycemic hypoxemia. These effects were much less striking than expected, based on earlier work in sheep (Shelley, Bassett & Milner, 1975; Robillard, Sessions, Kennedy & Smith, 1978). Although catecholamines increased significantly in response to hypoxemia both in hyperglycemic and euglycemic fetuses, the increase was less in the hyperglycemic group, possibly resulting from a modulating effect of the high glucose concentration on catecholamine release from the adrenal medulla. Finally, a significant fetal insulin response to hyperglycemia was seen which, suggestively, was partially inhibited in the presence of hypoxemia and its associated increase in sympathoadrenal activity.

Rounded atelectasis: a pulmonary pseudotumor.

Rounded atelectasis is a benign entity that is often misinterpreted as a pulmonary neoplasm. The roentgenologic appearance of a mass is due to an infolding of atelectatic tissue intermingled with pleura, blood vessels, and bronchi. Rounded atelectasis is usually asymptomatic and is commonly associated with chronic pleural disease or pleural effusions. The distinctive radiologic features include a rounded, pleural-based opacity associated with adjacent pleural thickening and volume loss of the affected lobe. The pathognomonic sign is the "comet tail" that results from the crowding of vessels and bronchi as they enter the atelectatic region. Many authors consider this constellation of findings diagnostic. Rounded atelectasis usually remains stable over time; however, slow growth, as well as diminution in size, has been described. A retrospective analysis revealed 7 cases of rounded atelectasis at our institution over a 9-year period. Three were operated on to exclude malignancy, one was confirmed at operation performed for other reasons, and 3 were followed up expectantly. We conclude that recognition of this entity and its radiologic features can be diagnostic and render further workup, including thoracotomy, unnecessary.

Sympathoadrenal responses during hypoglycemia, hyperinsulinemia, and hypoxemia in the ovine fetus.

Interrelations of sympathoadrenal function and changes in glucose and insulin homeostasis were studied in chronically cannulated late gestation fetal sheep. Catecholamine secretory rates (based on direct adrenal sampling) and plasma concentrations were determined in the fetus during 2 h of insulin-induced hypoglycemia, during a period of hypoxemia, and during hyperinsulinemia per se (i.e., without hypoglycemia). Fetal insulin infusion (5-10 mU.kg-1.min-1) resulted in hypoglycemia and a significant rise in secretion of epinephrine but not of norepinephrine. By contrast, fetal hypoxemia caused a prompt and significant increase in adrenal secretion of both norepinephrine and epinephrine. Changes in peripheral plasma catecholamine levels were usually, but not always, qualitatively similar to those in adrenal secretion; the latter was a far more sensitive indicator of adrenal function. Hyperinsulinemia per se caused no change in adrenal secretory rates or plasma concentrations of catecholamines. Nevertheless, insulin infusion caused a fetal tachycardia even in the absence of hypoglycemia and hypoxemia, suggesting either a direct effect on the heart or stimulation of sympathetic nerves.

Adrenal secretion of glucocorticoids during hypoxemia in fetal sheep.

This work was undertaken to investigate the fetal adrenal corticoid secretory response to hypoxic stress in late gestation. Experiments were performed in two groups of fetal sheep of different gestational ages, group I, 129-132 (mean, 130) days and group II, 135-139 (mean, 136) days. Fetuses were prepared with chronic adrenal cannulas as well as peripheral arterial and venous catheters. With the fetus at rest and after 7, 9, 11 and, in some instances, 30 and 60 min of hypoxia (maternal FIO2 10%), precisely timed (2 min) samples of adrenal effluent were collected for determination of cortisol (F) and corticosterone (B) secretion rates. Peripheral samples were obtained intermittently for blood gas and lactate determinations. Resting corticoid secretory rates were highly variable, suggesting an episodic secretory pattern. Corticoid secretory responses to hypoxemia were significantly elevated at 7-11 min, peaked at 30 min, and remained stable at 60 min. Specifically, in group I, F secretion increased from a baseline value of 37 +/- 19 ng/min to a peak hypoxemic response of 376 +/- 80 ng/min; B secretion increased from 6 +/- 4 to 170 +/- 32 ng/min. In group II, F secretion increased from 99 +/- 20 to 653 +/- 107 ng/min; B secretion increased from 12 +/- 5 to 200 +/- 28 ng/min. When related to adrenal gland weight, there was no difference between F secretory responses in groups I and II, whereas relative B secretory responses were lower in group II than in group I at 9 and 11 min of hypoxemia. We conclude that the 129-139 day sheep fetal adrenal cortex is highly sensitive to hypoxic stress with the effect presumably mediated by elevated levels of endogenous ACTH. The B stress response decreases as gestational age advances from the 129-132 day range to 135-139 days.

Management of esophageal injuries.

A multiinstitutional study of 39 esophageal injuries treated between 1982 and 1988 and a comprehensive review of the literature revealed an unacceptably high mortality rate of more than 20%. Results of the current study indicated that prompt diagnosis and aggressive surgical management of esophageal injuries could improve the outcome and lower the associated mortality. The clinical experience and literature review allowed us to elaborate caveats and principles that, if adhered to, should improve the outcome in esophageal injuries.

Plasma catecholamines in the hypoxaemic fetal rhesus monkey.

To assess the response of the sympathoadrenal system of the primate fetus to oxygen deprivation, we measured plasma catecholamines in 8 chronically catheterized fetal rhesus monkeys. A range of fetal hypoxaemia was produced by having the mother inspire 15, 10, or 9% oxygen mixtures while tranquilized with ketamine. Catecholamines from fetal carotid and maternal femoral arteries were measured by radioenzymatic assay. Fetal plasma norepinephrine and epinephrine concentrations increased significantly at all levels of hypoxaemia, but dopamine increased only at very low fetal oxygen tensions. Norepinephrine levels exceeded those of epinephrine and dopamine under all conditions. Relatively more severe hypoxaemia was necessary to elevate concentrations of epinephrine above baseline as compared with norepinephrine. A negative exponential correlation (P less than 0.001) was found between both fetal arterial PO2 and oxygen content and plasma norepinephrine and epinephrine, which was qualitatively similar to that observed previously in the sheep fetus. Maternal catecholamines were found to increase during hypoxaemia as well, but to a lesser degree than in the fetus.