John E. Fisher

Perfluorocarbon-associated gas exchange in gastric aspiration.

ObjectivesTo test whether perfluorocarbon-associated gas exchange (gas ventilation of the perfluorocarbon-liquid filled lung) could support oxygenation better than conventional positive pressure breathing in a piglet model of gastric aspiration-induced adult respiratory distress syndrome (ARDS). DesignProspective, randomized, blinded, controlled study. SettingA critical care research laboratory in a university medical school. SubjectsFourteen healthy piglets. InterventionsUnder α-chloralose anesthesia and metocurine iodide neuromuscular blockade, 14 piglets underwent tracheostomy; central venous, systemic and pulmonary arterial catheterizations; and volume-regulated continuous positive-pressure breathing. Homogenized gastric aspirate (1 mL/kg) titrated to pH of 1.0 was instilled into the tracheostomy tube of each subject at 0 min to induce ARDS. Hemodynamics, lung mechanics, and gas exchange were evaluated every 30 mins for 6 hrs. Seven piglets were treated at 60 mins by tracheal instillation of perflubron, a volume selected to approximate normal functional residual capacity, and were supported by perfluorocarbon-associated gas exchange without modifying ventilatory settings. Perflubron was added to the trachea every hour to replace evaporative losses. Measurements and Main ResultsThere was a significant difference in oxygenation over time when tested by repeated-measures analysis of variance (F test = 8.78, p < .01). On further analysis, the differences were not significant from baseline to 2.5 hrs but became increasingly significant from 2.5 to 6 hrs after injury (p < .05) in the inflammatory phase of gastric aspiration-induced ARDS. Histologic evidence for ARDS in the treated group 6 hrs after injury was lacking. ConclusionsIn the piglet model, perfluorocarbon-associated gas exchange with perflubron facilitates oxygenation in the acute phase of gastric aspiration-induced inflammatory ARDS when compared with conventional positive-pressure breathing. Histologic and physiologic data suggest that perfluorocarbon-associated gas exchange with perflubron might prevent ARDS if instituted after aspiration in the time window before the acute inflammatory process is manifest. (Crit Care Med 1994; 22:1445–1452)

Perfluorocarbon-associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome

OBJECTIVE To compare the effectiveness of perfluorocarbon-associated gas exchange to volume controlled positive pressure breathing in supporting gas exchange, lung mechanics, and survival in an acute lung injury model. DESIGN A prospective, randomized study. SETTING A university medical school laboratory approved for animal research. SUBJECTS Neonatal piglets. INTERVENTIONS Eighteen piglets were randomized to receive perfluorcarbon-associated gas exchange with perflubron (n=10) or volume controlled continuous positive pressure breathing (n=8) after acute lung injury was induced by oleic acid infusion (0.15 mL/kg iv). MEASUREMENTS AND MAIN RESULTS Arterial and venous blood gases, hemodynamics, and lung mechanics were measured every 15 mins during a 3-hr study period. All animals developed a metabolic and a respiratory acidosis during the infusion of oleic acid. Following randomization, the volume controlled positive pressure breathing group developed a profound acidosis (p<.05), while pH did not change in the perfluorocarbon-associated gas exchange group. Within 15 mins of initiating perfluorocarbon-associated gas exchange, oxygenation increased from a PaO2 of 52 +/- 12 torr (6.92 +/- 1.60 kPa) to 151 +/- 93 torr (20.0 +/- 12.4 kPa) and continued to improve throughout the study (p<.05). Animals that received volume controlled positive pressure breathing remained hypoxic with no appreciable change in PaO2. Although both groups developed hypercarbia during oleic acid infusion, PaCO2, steadily increased over time in the control group (p<.01). Static lung compliance significantly increased postrandomization (60 mins) in the animals supported by perflurocarbon-associated gas exchange (p<.05), whereas it remained unchanged over time in the volume controlled positive pressure breathing group. However, survival was significantly higher in the perfluorocarbon-associated gas exchange group with eight (80%) of ten animals surviving the entire study period. Only two (25%) of the eight animals in the volume controlled positive pressure breathing group were alive at the end of the study period (log-rank statistic, p=.013). CONCLUSIONS Perflurocarbon-associated gas exchange enhanced gas exchange, pulmonary mechanics, and survival in this model of acute lung injury.

Triad of Hypopituitarism, Granulomatous Hypophysitis, and Ruptured Rathke's Cleft Cyst

A 19-year-old girl with pituitary insufficiency and a large sella turcica was found to have granulomatous hypophysitis in association with a Rathkes cleft cyst. We think that the inflammatory process represents a foreign body reaction to leakage of cyst contents, with destruction of pituitary tissue.

Mechanical performance of clinically available, neonatal, high-frequency, oscillatory-type ventilators

OBJECTIVE To perform a functional evaluation of five different high-frequency, oscillatory-type ventilators that are currently being marketed for neonatal high-frequency oscillation. DESIGN Observational animal study. SETTING Laboratory. SUBJECTS New Zealand White male rabbits. INTERVENTIONS Oscillator waveforms and delivered volumes were measured plethysmographically for the following ventilators: the SensorMedics 3100 A; the Dräger Baby Log 8000; the Metran Humming V; the Infant Star; and the Infant Star 950. The independent variables which were adjusted included frequency (5 to 15 Hz), amplitude (25% to 100%), mean airway pressure (5 to 25 cm H2O) and lung injury. MEASUREMENTS AND MAIN RESULTS At 15 Hz, the volume delivered at the 100% amplitude setting varied from 2.1 to 8.8 mL. Generally, the delivered volume decreased with increasing frequency, and with increased percentage of amplitude. Volume delivery was relatively unaffected by mean airway pressure but decreased with lung injury. Waveforms ranged from pure sinusoidal to a complex square wave. The handling of inspiration/expiration time ratios was ventilator specific. The SensorMedics inspiration/ expiration ratio is user selected over a range from 1:2.3 (30% inspiratory time) to 1:1 (50% inspiratory time) and once selected it is consistent over its entire range of operating frequencies. The Drager ratio is machine determined and varied from 1:2.5 at 5 Hz to 1:1 at 15 Hz. Inspiratory time of the Infant Star is machine set at 18 msecs such that the inspiration/expiration ratio is 1:10.1 at 5 Hz and 1:2.7 at 15 Hz. The Humming V has a fixed inspiration/expiration ratio of 1:1. The relationship of the mean airway pressure displayed on the ventilator to the alveolar occlusion pressure varied considerably among devices. The displayed mean pressure could either overestimate (SensorMedics at 33% inspiratory time or Infant Star), approximate (Humming V), or underestimate (Dräger) the mean lung distending pressure measured during a brief occlusion maneuver. CONCLUSIONS The findings demonstrate large variations in machine performance. The ventilators also differed profoundly in complexity of operation and versatility as neonatal ventilators.

Autoimmune disorders complicating adolescent hodgkin's disease

Four adolescents with Hodgkins disease also developed autoimmune diseases. There were two idiopathic thrombocytopenic purpura (ITP), one polymyositis, and one scleroderma. The first two patients developed ITP in the absence of a spleen, and with their Hodgkins disease in remission. The first patient with Hodgkins disease has been continuously free of cancer for over five years. The second patient was a 17‐year‐old male whose Hodgkins disease recurred, but whose disease was in remission at the time the ITP occurred. The polymyositis occurred in an 18‐year‐old youth when he was in his initial remission for his Hodgkins disease, but his disease subsequently recurred two years later. This youth presented with Coombs positive autoimmune hemolytic anemia. The polymyositis did not respond to therapy, and he is left with severe muscle wasting and weakness; however, the polymyositis is now quiescent. The scleroderma occurred in an 18‐year‐old female who had been continuously free of Hodgkins disease for eight years. The scleroderma did not respond to drug therapy and she now has moderate skin changes, but remains in continuous remission of her Hodgkins disease. Although there are a few reports of Hodgkins disease and concurrent autoimmune disorders, physicians dealing with cancer in adolescents should be aware of this association.

Further evidence of a decorin-collagen interaction in the disruption of cervical collagen fibers during rat gestation.

OBJECTIVE Our purpose was to determine the histologic distribution and expression of decorin in rat cervix throughout the course of rat gestation and to correlate the findings with the known progression of collagen fiber disruption and cellular turnover in this tissue. STUDY DESIGN Cervices from pregnant animals at 5, 11, 18, and 21 days were studied. A proteoglycan of low molecular weight, decorin, was detected by sensitive and specific immunohistochemical analysis with a biotin-avidin horseradish peroxidase method. RESULTS Decorin was not detected on day 5. By day 11 moderate decorin staining was detected in the subepithelial layer and in the deep stroma. Decorin staining progressed to a strong expression in the subepithelial layer and to a moderate expression in the deep stroma on day 18. On day 21 (term in rat) the staining was fairly homogeneous throughout the connective tissue stroma. CONCLUSION These findings clearly demonstrate that decorin expression increased progressively throughout pregnancy and are consistent with the hypothesis that an excess of decorin near term is capable of initiating a decorin-collagen interaction that leads to collagen fibril disruption and decreased cervical tensile strength.

Lipoblastoma : better termed infantile lipoma?

Abstract Lipoblastoma is a rare adipose tumor occurring exclusively in childhood. There have been no reports of metastases, making the designation “blastoma” confusing, since this term is usually reserved for malignant tumors. Two recent cases treated at our institution confirm its benign nature. In addition, a review of the literature supports the idea that the tumor may more accurately be described as an “infantile lipoma”. Infantile lipoma better reflects many of the tumors characteristics such as, its early occurrence, its ability to mature into a simple lipoma, its cellular composition of mainly mature adipocytes, and its benign course. Although lipoblastoma is an uncommonly encountered tumor, making an effort to change its name to infantile lipoma will result in a more a accurate term that will facilitate treatment.

Effect of rotavirus infection and malnutrition on uptake of a dietary antigen in the intestine.

ABSTRACT: Intestinal absorption of ovalbumin (OVA), a dietary macromolecule, was studied in malnourished and normally nourished suckling mice after experimentally induced infection with rotavirus. All mice developed diarrhea within 24 to 48 h postinoculation. The malnourished animals exhibited more severe symptoms and an increased number of rotavirus-containing enterocytes in intestinal sections as compared to well-nourished mice when examined 3 d postinoculation, at the peak of diarrhea. Histopathologic examination revealed villus atrophy and pronounced vacuolization of villus enterocytes in association with malnutrition and rotavirus infection. The combination of malnutrition and viral infection resulted in more severe mucosal damage, including disruption of microvillus borders. After a single oral dose of 100 μg OVA at 3 d postinoculation, the concentration of OVA in serum, gastric content, intestinal lavage fluid, and intestinal tissue homogenates was measured at different time intervals. The concentrations of OVA in intestinal tissue were significantly higher in malnourished animals, whereas lower values were found in rota virus-infected animals. In all mice, OVA was rapidly absorbed and could be consistently detected in the serum within 5 min. OVA levels peaked at 45 to 60 min and then gradually declined. In malnourished infected animals, the uptake of OVA was rapid and resulted in significantly higher serum levels when compared to well nourished or uninfected controls, respectively. The peak uptake of OVA per g body wt was about 4.5 times more in malnourished infected compared to well-nourished infected mice and 2.5 times higher in normally nourished infected animals when compared to uninfected controls. These results indicate that rotavirus infection in association with malnutrition may cause a significant rise in gut permeability to environmental macromolecules.

Ectasia of the Rete Testis with Ipsilateral Renal Agenesis

Scrotal masses are a common problem in children. Cystic lesions usually are found to be hydroceles, while solid masses suggest the possibility of neoplasia. A rare cause of a cystic scrotal mass is ectasia of the rete testis. A review of the literature reveals only 1 case similar to the patient herein described. Both patients had agenesis of the ipsilateral kidney, which explained on the basis of the embryologic overlapping of the genitourinary system. Our patient bears clinical similarity to the ACI rat and correlation is made with this animal model system. Excision of the multiloculated rete testis cyst, rather than orchiectomy, appears to be curative.

The use of different induction and maintenance chemotherapy regimens for the treatment of advanced yolk sac tumors.

Four children with yolk sac tumor were treated with an aggressive combination chemotherapy program. Three children had presacral primary tumors, one having pulmonary metastases, and one had a testicular primary tumor with pulmonary metastases. Three children were treated when they had measurable disease, and one had no measurable disease. The chemotherapy program consisted of a 6-wk induction period with vincristine (VCR), cis-diamminedichloroplatinum (DDP), and bleomycin. Maintenance therapy consisted of VCR, actinomycin D, and cyclophosphamide (cytoxan) every 3-4 wk as tolerated. Treatment was discontinued after 12 mo of complete remission. All three patients with evaluable disease had a partial response (PR) to induction therapy. Two underwent surgical exploration following induction therapy, one a laparotomy and the other a thoracotomy, and were found to have only scar tissue at the sites of presumed residual disease. The third child with measurable disease progressed to a clinical complete response (CR) during maintenance therapy. Two patients have had no evidence of disease (NED) for 42+ and 41+ mo since starting therapy (28+ and 27+ mo since completing treatment). Two patients are NED 11+ and 7+ mo since starting therapy and remain on treatment. We have encountered no significant renal or pulmonary toxicity, and there have been only two hospitalizations during maintenance therapy for fever and neutropenia. These preliminary results employing different induction and maintenance chemotherapy programs and planned second-look surgical intervention appear encouraging.