Postnatal human lung growth.

Standard morphometric methods were applied to the lungs of 36 boys and 20 girls aged from 6 weeks to 14 years, dying as a result of trauma or after short illnesses. Individual lung units, alveolar dimensions, and number of alveoli per unit area and volume did not differ between boys and girls, but boys had bigger lungs than girls for the same stature. This resulted in a larger total number of alveoli and a larger aveolar surface area in boys than in girls for a given age and stature. There may be more respiratory bronchioles in boys than girls. There was rapid alveolar multiplication during the first two years of life and alveolar dimensions and number of alveoli per unit area and volume did not change much during this period. There was little or no increase in the total number of alveoli after the age of 2 years but the data are hard to interpret. There is a wide scatter of the total number of alveoli in the growing lung, in keeping with the observation that the total number of alveoli is very variable in adults. Prediction data are given for the various morphometric variables studied.     

The microanatomy of the alveolar duct system

Observations made on wet and dry slices of inflated human lungs taken at necropsy have been used to give a more complete account of the alveolar duct system, the basic respiratory structure. This includes consideration of the central spiral alveolar duct fibre, which is thought to consist of elastic and collagen, the spiral arrangement of alveoli and the special nature of the terminal alveolus, the interdigitation of alveoli from adjacent alveolar ducts and the arrangement of pulmonary arterioles. This suggests that the alveolar duct system is specifically designed so that changes in volume are not accompanied by changes in alveolar surface area.     

Measurement of respiratory function: gas exchange

Oxygen passes from the atmosphere to the cells along a concentration gradient (down a cascade) via the alveoli, the arteries and the capillaries. Arterial (and thus cellular) oxygenation depends on the efficient matching of ventilation with pulmonary blood flow. Over-perfused and under-ventilated or non-ventilated alveoli lead to hypoxaemia and over-ventilated, under-perfused alveoli to wasted ventilation (dead space). The average (or ideal) partial pressure of oxygen in arterial blood can be calculated. Gas exchange and its impairments can be assessed from measurements of gas volumes and partial pressures in arterial and mixed venous blood and in expired air. Alveolar-arterial gradients, pulmonary shunt and physiological dead space can all be calculated. There are more complex and sophisticated ways of assessing gas exchange, such as scanning blood flow and ventilation with radionuclides and the use of gases with varying solubilities to assess gas exchange, but these are not commonly used in clinical anaesthetic practice.     

Role of Homeobox Genes in Normal Mammary Gland Development and Breast Tumorigenesis

The role of homeobox-containing genes in embryogenesis and organogenesis is well documented. Also, a sizeable body of evidence has accumulated and supports the fact that homeobox genes, when dysregulated, are involved in tumorigenesis. However, the precise mechanisms of homeobox gene functions are largely unknown. The mammary gland, in which most maturation occurs postnatally, provides an ideal model for studying the functions of homeobox genes in both development and tumorigenesis. The expression of many homeobox genes has been detected in both normal mammary gland and neoplastic breast tissues. In the normal mammary gland, the expression of homeobox genes is coordinately regulated by hormone and extracellular matrix (ECM) and other unknown factors in a spatial and temporal manner in both stromal and epithelial cells. Animals with misexpressed homeobox genes displayed different extents of defects in ductal proliferation, side branching, and alveoli formation, implying that homeobox genes are important for normal mammary gland development. Recent studies of homeobox genes in breast cancer cells and primary tumors indicate that they may also play a contributory or causal role in tumorigenesis by regulating the cell cycle, apoptosis, angiogenesis, and/or metastasis.     

Spannungspneumoperikard als seltene Komplikation bei schwerem Polytrauma

Thoracic injury is a relevant and common complication in multiply injured patients. Typical patterns of injury comprise rib fractures, serious lung trauma as well as diaphragmatic and aortic rupture. In contrast, posttraumatic tension pneumopericardium following blunt thoracic trauma is a very rare complication. However, if unrecognized it might provoke cardiac tamponade and death. For the development of a pneumopericardium, free air follows the vessel bundles up to the pericardium. Hence, if the number of ruptured alveoli is high, or these alveoli are placed close to the heart, and if additional risk factors, such as high inspiratory ventilation pressure, are present, a tension pneumopericardium can induce cardiac tamponade. The aim of this report is to illuminate diagnostic and therapeutic strategies for posttraumatic pneumopericardium by presentation of a case from our trauma centre and a critical discussion of the present literature.     

'Alveolar recruitment strategy' improves arterial oxygenation during general anaesthesia

Abnormalities in gas exchange during general anaesthesia are caused partly by atelectasis. Inspiratory pressures of approximately 40 cm H2O are required to fully re-expand healthy but collapsed alveoli. However, without PEEP these re-expanded alveoli tend to collapse again. We hypothesized that an initial increase in pressure would open collapsed alveoli; if this inspiratory recruitment is combined with sufficient end-expiratory pressure, alveoli will remain open during general anaesthesia. We tested the effect of an 'alveolar recruitment strategy' on arterial oxygenation and lung mechanics in a prospective, controlled study of 30 ASA II or III patients aged more than 60 yr allocated to one of three groups. Group ZEEP received no PEEP. The second group received an initial control period without PEEP, and then PEEP 5 cm H2O was applied. The third group received an increase in PEEP and tidal volumes until a PEEP of 15 cm H2O and a tidal volume of 18 ml kg-1 or a peak inspiratory pressure of 40 cm H2O was reached. PEEP 5 cm H2O was then maintained. There was a significant increase in median PaO2 values obtained at baseline (20.4 kPa) and those obtained after the recruitment manoeuvre (24.4 kPa) at 40 min. This latter value was also significantly higher than PaO2 measured in the PEEP (16.2 kPa) and ZEEP (18.7 kPa) groups. Application of PEEP also had a significant effect on oxygenation; no such intra-group difference was observed in the ZEEP group. No complications occurred. We conclude that during general anaesthesia, the alveolar recruitment strategy was an efficient way to improve arterial oxygenation.      

Electron microscopy of desquamative interstitial pneumonia

The clinical, radiographical, and physiological picture of two patients suffering from desquamative interstitial pneumonia is described. The diagnosis was established by lung biopsy when the characteristic histological features were found on light microscopy. The dramatic response to adequate corticosteroid therapy is recorded, and attention is directed to the danger of serious relapse on early withdrawal of this treatment and the subsequent satisfactory response to a second course. Electron microscopical studies of the tissue from one patient add materially to the understanding of the clinical course and the nature of the tissue response. At the ultrastructural level the attenuated membranous (type 1) pneumonocytes which normally line the alveoli were replaced by granular (type 2) pneumonocytes. The desquamated intra-alveolar cells comprised two main groups. These were granular pneumonocytes, similar to those lining the alveoli, and smaller numbers of macrophages. The cytopathic effects of virus infection were not detected by light or electron microscopy.     

Value of measurement of alveolo-arterial gradient of PCO2 compared to pulmonary scan in diagnosis of thromboembolic pulmonary disease

The alveolo-arterial gradient of Pco₂ was measured and the percentage of ventilated but unperfused alveoli was derived from Severinghaus''s formula in 312 patients divided into five groups according to clinical symptoms, biological, radiographic, scintigraphic or pathological data—87 patients with proved thromboembolic disease, 41 with probable thromboembolic disease, 67 with possible thromboembolic disease, 101 with non-embolic pulmonary disease, and 16 cases of miscellaneous cardiac diseases. After all capnographic curves without an alveolar plateau had been eliminated, 223 capnograms (71%) were examined.In 59% of the patients with proved thromboembolic disease, the percentage of ventilated but unperfused alveoli was abnormal (>15%). In this group the mean percentage of ventilated but unperfused alveoli (16·3%) was significantly different from the value obtained in the remaining groups. This test was positive in 40% of the patients with probable thromboembolic disease but it was also positive in 22·5% of the cases of miscellaneous pulmonary and cardiac non-embolic diseases.Compared to the lung scan, this method was less sensitive but also less equivocal in patients with preexisting cardiopulmonary disorders. Estimates of the pulmonary vascular defect by these two methods did not always correspond.     

Hashimoto's disease (struma lymphomatosa)

Hashimoto's disease is characterized by a diffuse, resilient enlargement of the thyroid gland. The pathological condition is confined within the capsule and there is little or no adherence to surrounding structures. The fibrous trabeculae produce a lobulated appearance and may account for a preoperative impression of adenomatous goiter. Microscopically, the distinguishing features consist of degeneration and disappearance of the alveoli due to marked lymphocytic infiltration. Where masses of lymphocytes have coalesced, germinal follicles may be seen. Moderate fibrosis is present, tending to form bands. The alveoli are atrophic and compressed. Atrophic, degenerated alveoli with their coalesced nuclei may easily be confused with giant cells.     

Surgical drainage of lactational breast abscess with ultrasound‐guided Encor vacuum‐assisted breast biopsy system

Lactational breast abscess is a serious complication of mastitis and commonly diagnosed in breast‐feeding women. The traditional drainage of breast abscess was often performed with incisive technique which may result in prolonged healing time, regular dressings, dressing pain, interfering with breastfeeding and unsatisfactory cosmetic outcome. As minimal invasive alternatives to incisive drainage, needle aspiration or percutaneous catheter placement cannot completely replace incisive drainage for the inability to treat large, multiloculated or chronic abscess. Vacuum‐assisted breast biopsy system (VABB) has been successfully applied in the treatment of benign breast diseases with satisfactory cosmetic outcomes. Among VABB devices, EnCor system has some distinctive features that make it an appropriate candidate for the treatment of lactational breast abscesses. In this study, for the first time, we investigated the feasibility, efficacy, and cosmetic results of surgical drainage of lactational breast abscess with US‐guided Encor VABB system. Our data suggests this procedure could serve as a promising alternative for women with lactational breast abscess who require incisive intervention with high cure rate, relatively short healing time, low recurrence rate, few complications, satisfactory cosmetics outcome and without interfering with breastfeeding.     

Hormone Replacement Therapy and Breast Cancer Today: Awaiting the Women's Health Initiative Results

Abstract: The available data on whether or not estrogen replacement therapy is a significant cause of breast cancer remains in conflict. There is an apparent survival benefit to women whose breast cancer is diagnosed while on hormones. Giving hormone replacement to breast cancer survivors has no significant detrimental effect. Designer estrogens and phytoestrogens appear to be potential antagonists to breast and uterine epithelium, while offering agonist protection to bone and the cardiovascular system. Hopefully data from the Women's Health Initiative project scheduled to end in 2003 will shed more light on this issue.     

Prostatic hyperplasia and neoplasia in aging F344 rats

The prostates of 1775 (614 control and 1161 experimental) 2-year-old F344 rats from 12 different carcinogen bioassays conducted by the Bioassay Program of the NCI and the NTP were evaluated histologically. The incidence of prostatic lesions including (atypical) hyperplastic foci, adenomas, and carcinomas was 6.8%. There was no difference in the type or incidence of the lesions between treated and untreated animals. Adenomas or carcinomas were found in 71 (4.0%) of the rats, primarily as incidental findings. The number of tumors and hyperplastic foci varied from laboratory to laboratory depending on the anatomical localization of the plane of the section. Most of the neoplasms were found in the ventrolateral lobes of the prostate (ventral prostate). When adequate sections were prepared of the ventral lobe, 10-20% of the prostates had these proliferative lesions. The lesions were usually small and originated in the epithelium of the alveoli and small ducts and were usually small and originated in the epithelium of the alveoli and small ducts and were not associated with the common inflammatory lesions of the rat prostate. Thin fibrous capsules were formed in a few of the larger tumors. Metastases were not observed but there was local invasion into alveoli, ducts and interstitial connective tissue. Evidence is presented that the atypical hyperplasias progress to adenoma and carcinoma. The F344 rat offers a potential model for the study of latent prostatic preneoplastic and neoplastic lesions.     

Growth potential of the immature transplanted lung. An experimental study

Syngeneic (Lewis to Lewis) and allogeneic (Brown Norway to Lewis) unilateral left lung transplants were performed on immature rats at 6 weeks of age at a time when alveoli are still multiplying after birth. Left lung denervation without transplantation was performed in a further group of rats (Lewis) by stripping the hilum, at 4 and 6 weeks of age. Animals were killed at either 2 weeks or 6 months after operation. Right and left lungs were analyzed separately by light microscopic quantitative techniques and findings were compared with findings from control animals matched for age and strain. The transplanted left lung in both syngeneic and allogeneic animals continued to grow to a normal size by formation of new alveoli, despite the presence of low-grade rejection activity in the immunosuppressed allogeneic group. The airways showed an increase in diameter for age at the hilum and periphery (p less than 0.01 and less than 0.001, respectively). The volume of the contralateral right lung was greater than normal because of an increase in number (p less than 0.01) and size of alveoli for age. Denervation alone was associated with normal growth of both lungs. Thus it appears that, in rats, the transplanted immature lung can fulfill its growth potential.     

Role of Ets transcription factors in mammary gland development and oncogenesis

PEA3 is the founding member of a subfamily of closely related ets genes that includes ER81 and ERM. PEA3 is expressed in the epithelial cells of mammary buds at the time that these first appear during mouse embryogenesis, and it is differentially expressed during postnatal mammary gland development. PEA3 expression is highest at the onset of puberty and during early pregnancy, times of extensive epithelial outgrowth and branching. PEA3 is expressed in undifferentiated epithelial cap cells of terminal end buds, and in differentiated myoepithelial cells of ducts and alveoli. Loss-of-function mutations in the PEA3 gene compromise mammary ductal branching at the onset of puberty and early during pregnancy. PEA3 is overexpressed in the vast majority of human breast tumors and in nearly all of the HER2-positive subclass of such tumors. PEA3 is similarly overexpressed in transgenic mouse models of this malignancy. Expression of dominant-negative PEA3 in the mouse mammary gland of MMTV-HER2 transgenic mice dramatically delays the onset and reduces the incidence of mammary tumors. Hence PEA3 and/or its close relatives play key regulatory roles in both mammary gland development and oncogenesis.     

A NEW APPROACH TO ARTIFICIAL EXPANSION AND VENTILATION OF THE LUNG IN THE SEVERELY ASPHYXIATED NEONATE

In severe asphyxia, expansion of the newborn lung must precedeventilation by intermittent positive pressure. Inadequate expansionmay lead to hypoxia and excessive expansion to rupture of thelung. The only way in which a predetermined pressure can beachieved, and not exceeded in the alveoli, is by applying thatpressure at the mouth and waiting until all flow ceases. Applyingpressure in this way and increasing it according to a "staircase"pattern, with appropriate steps at suitable intervals, shouldensure that the maximum pressure produced in the alveoli isno greater than the minimum necessary for resuscitation in eachindividual infant. On the basis of published work, ranges ofoptimum values for the increments and time intervals are suggested.Clinical judgement is still necessary to select from withinthese ranges, but this "pressure staircase" method should providea systematic approach to the problem. A suitable apparatus isdescribed.     

Visual validation of the mechanical stabilizing effects of positive end-expiratory pressure at the alveolar level

BACKGROUND: Positive end-expiratory pressure (PEEP) reduces ventilator-induced lung injury (VILI), presumably by mechanically stabilizing alveoli and decreasing intrapulmonary shear. Although there is indirect support for this concept in the literature, direct evidence is lacking. In a surfactant depletion model of acute lung injury we observed unstable alveolar mechanics referred to as repeated alveolar collapse and expansion (RACE) as measured by changes in alveolar area from inspiration to expiration (I - E(Delta)). We tested the hypothesis that over a range of tidal volumes PEEP would prevent RACE by mechanically stabilizing alveoli. MATERIALS AND METHODS: Yorkshire pigs were randomized to three groups: control (n = 4), Tween (surfactant-deactivating detergent) (n = 4), and Tween + PEEP (7 cm H(2)O) (n = 4). Using in vivo video microscopy individual alveolar areas were measured with computer image analysis at end inspiration and expiration over consecutive increases in tidal volume (7, 10, 15, 20, and 30 cc/kg.) I - E(Delta) was calculated for each alveolus. RESULTS: Surfactant deactivation significantly increased I - E(Delta) at every tidal volume compared to controls (P < 0.05). PEEP prevented this change, returning I - E(Delta) to control levels over a spectrum of tidal volumes. CONCLUSIONS: RACE occurs in our surfactant deactivation model of acute lung injury. PEEP mechanically stabilizes alveoli and prevents RACE over a range of tidal volumes. This is the first study to visually document the existence of RACE and the mechanical stabilizing effects of PEEP at the alveolar level. The ability of PEEP to stabilize alveoli and reduce shear during mechanical ventilation has important implications for therapeutic strategies directed at VILI and acute respiratory distress syndrome.     

Lung structure and function in cigarette smokers.

BACKGROUND--Cigarette smoking produces an inflammatory response in the airways of everyone but only 15-20% of smokers develop airways obstruction. The present study concerns the relative importance of peripheral airways inflammation and the emphysematous destruction of the parenchymal support of the airways in the pathogenesis of this obstruction. METHODS--A total of 407 patients with a diagnosis of lung tumour performed pulmonary function tests a day or two before a lung or lobar resection. The specimens were fixed in inflation and analysed at the gross and microscopic level to determine the extent and severity of the emphysematous process, the number of alveoli supporting the outer walls of the airways, and the average distance between alveolar walls. The severity of the inflammatory process in the respiratory and nonrespiratory bronchioles was also assessed using a previously established grading system. RESULTS--The lung function test showed that a decline in FEV1 was associated with an increase in residual volume and a decrease in the diffusing capacity for carbon monoxide and a reduction in the lung maximum elastic recoil pressure. The prevalence of grossly visible emphysema increased as FEV1 declined, but the extent and severity of these lesions and the number of alveoli supporting the outer walls of the peripheral airways was similar at all levels of FEV1. The system used to grade inflammatory response in the peripheral airways failed to identify a specific defect responsible for the physiological abnormalities. CONCLUSION--The reduction in FEV1 associated with chronic cigarette smoking can be partially explained by loss of lung elastic recoil pressure which reduces the force driving air out of the lung. This loss of elastic recoil pressure is attributed to microscopic enlargement of the air spaces rather than to grossly visible emphysema. The exact nature of the lesions responsible for the peripheral airways obstruction remains to be identified.     

Respiration: gas transfer

The principles of gas transfer between the atmosphere and cell mitochondria can be considered in a number of steps: inspired gases are humidified in the upper airways and mix with expired gases in the alveoli. In perfused alveoli, gases then diffuse passively down a partial pressure gradient into pulmonary capillary blood. Gases are transported by the blood, in a dissolved state or by specific transport systems, to the systemic capillaries from where they diffuse into cells. Efficient gas exchange between the atmosphere and mitochondria requires the transfer of large volumes of gas with minimal reduction in partial pressure. The nature of oxygen binding to haemoglobin and the transport of carbon dioxide as bicarbonate in the blood improve the body’s ability to transfer these gases. An understanding of how anaesthetic gases are transferred to their site of action and why side effects occur is important to the safe conduct of anaesthesia.     

High-frequency jet ventilation through a fibreoptic bronchoscope channel during lung lavage

Simple manual ventilation facilitates removal of intra-alveolar accumulations. High-frequency jet ventilation can be performed through a narrow lumen like that of a fibreoptic bronchoscope. Accordingly, we expected that high frequency jet ventilation through a fibreoptic bronchoscope channel would facilitate lung lavage, and we developed a new bronchoalveolar lavage system, in which high-frequency jet ventilation through the channel of a fibreoptic bronchoscope was combined with conventional bronchoalveolar lavage. We describe a case in which this new lavage system, unlike conventional bronchoalveolar lavage, successfully removed the lipid material in the alveoli associated with pulmonary alveolar proteinosis.     

Extra-abdominal desmoid tumour of the breast: review of the primary management and the implications for breast reconstruction.

This case report illustrates the presentation and management of an extra-abdominal desmoid tumour of the breast. A review of the literature describing the aetiology, pathology and risk of recurrence was undertaken to determine how current understanding of this rare tumour may affect the management of patients, should they require breast reconstruction after radical excision of the primary tumour. The natural progression of the disease is variable and there are no markers predictive of recurrence or regression. Primary lesions should be assessed with respect to their anatomical site of origin (i.e. whether they arise within the breast or invade the breast from the underlying musculo-aponeurotic tissue) and the extent of local invasion. Radical excision of the tumour with clear histological margins decreases the likelihood of recurrence. Tumours arising from the musculo-aponeurotic system have increased risks of recurrence and of developing multifocal primary tumours in specific anatomical territories. Local recurrences should be assessed for extent and anatomical distribution, and radical excision performed as for a primary tumour. Radiotherapy can be used as an alternative treatment if radical excision of a primary or recurrent tumour would cause severe functional loss or mutilation. Radiotherapy can be used for positive histological margins following tumour excision. There is a higher risk of recurrence in the first 3 years after primary excision, and breast reconstruction may be best delayed for this period. Surgical trauma has been implicated in the aetiology of recurrence and the patient should be informed of this prior to breast reconstruction.