Candiduria in intensive care units: association with heavy colonization and candidaemia.

Candiduria is increasingly detected in intensive care unit (ICU) patients and often coexists with candidal colonization at other anatomical sites. Studies involving surgical and medical ICU patients have consistently reported a relationship between candiduria and heavy colonization. This suggests that candiduria could be considered as a marker for heavy colonization. Risk factors that predispose to heavy colonization are generally similar to those predisposing to candidaemia. Candiduria in ICU patients is characterized by a high mortality, largely through a significant relationship with candidaemia, which in some patients may reach 50%. Therapeutic interventions should be strongly considered in the critically ill patient who presents with candiduria and concurrent clinical risk factors predisposing to dissemination.

Pathogenesis of pulmonary infarction.

Pulmonary embolism discovered at autopsy is still as prevalent as previously reported in the last three to four decades. Only a certain percentage of pulmonary emboli result in pulmonary infarction. Recently published studies have suggested that importance of the size of the occluded pulmonary artery in the occurrence of infarction. Our study of 45 autopsy subjects in which there were pulmonary emboli shows a 31 percent incidence of pulmonary artery branches of 3 mm in diameter or less, but emboli in larger arteries may show frequent extensions into their smaller distal branches without producing infarct. Pulmonary infarction also occurs more commonly in patients dying of cardiovascular or malignant diseases than it does in those dying of other diseases, and the combination of shock and congestive left heart failure appears to be the most significant hemodynamic risk factor in the development of pulmonary infarction. However, the increased risk of pulmonary infarction in patients with malignancy may not be accounted for by the existence of these two hemodynamic risk factors alone.

Superior vena caval obstruction. Is it a medical emergency?

With the question in mind is superior vena caval obstruction a medical emergency, we reviewed 107 cases of superior vena caval obstruction in adult patients. We sought details of the time duration between the onset of symptoms and the treatment, and examined the complication and survival of patients with this disorder. Fifteen percent of the cases developed from benign causes. In 41 percent there was a previously recognized disease as the etiology. Benign disorders required longer to make the diagnosis. No serious complication resulted from the superior vena caval obstruction itself nor investigative procedures leading to the diagnosis despite, in some cases, a prolonged period between the onset of symptoms and the initiation of therapy. Prognosis and response to treatment were dependent on the underlying cause of the superior vena caval obstruction. Although several cases of tracheal obstruction were included in this series, we did not address the question of whether tracheal obstruction is or is not a medical emergency. No support was found for the notion that superior vena caval obstruction in itself represents a radiotherapeutic emergency.

Vasoactive intestinal peptide enhances lung preservation.

The outcome of lung transplantation is often dependent on the quality of the donor lungs. To explore a way to improve lung preservation, vasoactive intestinal peptide (VIP) was added to pneumoplegic solutions. The 4 solutions tested were Krebs solution, Krebs solution with VIP, University of Wisconsin solution, and the University of Wisconsin solution with VIP. The lungs of 8 male Sprague-Dawley rats were flushed and stored in these solutions for 24 hr. At regular intervals, tissue was sampled and examined by light, scanning, and transmission electron microscopy. Casts of the vasculature were made after 4 hr and viewed by a scanning electron microscope. Lungs appeared well preserved by light microscopy at all intervals. Although inflammatory cells around arteries, arterial constriction, bronchiolar epithelial detachment, peribronchiolar edema, and alveolar size inhomogeneity were greater with time, there was no significant difference among the 4 groups by light microscopy. Scanning microscopy of tissue at 24 hr confirmed the information found on light microscopy but did not allow separation of the groups. The vascular casts showed that edema around large vessels was less in the lungs treated with VIP (P < 0.01). Transmission electron microscopy showed that lungs stored in the solutions with VIP had significantly more normal-shaped mitochondria, less mitochondrial edema, less distortion of mitochondrial cristae, thinner basal lamina, and less aggregation of nuclear chromatin at most intervals sampled after 4 hr. We conclude that VIP added to certain pneumoplegic solutions improves the ultrastructure of rat lung stored in the cold for up to 24 hr. VIP may be an important additive to pneumoplegic solutions to improve preservation of lung before transplantation.

Giant cell arteritis manifesting as chronic cough and fever of unknown origin.

A 57-year-old white man sought medical attention because of chronic cough and fever of unknown origin. An extensive work-up over 4 weeks, including repeated blood cultures, chest roentgenograms, a gallium scan, and computed tomographic scans of the sinuses, chest, and abdomen, was nondiagnostic. The patient was referred to our institution for bronchoscopy. Further analysis of his history revealed that he had a headache in conjunction with the cough and an episode of a flashing color design in his left eye 1 week before assessment. The erythrocyte sedimentation rate was 115 mm in 1 hour. A biopsy of the temporal artery showed granulomatous inflammation of the vessel wall with multinucleated giant cells, histiocytes, lymphocytes, plasma cells, and few eosinophils. The multinucleated giant cells were closely related to the fragmented elastic lamina. Corticosteroid therapy resulted in prompt resolution of the chronic cough and fever. Giant cell arteritis should be considered in the differential diagnosis of chronic cough.

The G syndrome: a case report.

A case of the G syndrome is reported in a baby boy who had an unusual facies (prominent forehead, telecanthus, posteriorly rotated ears, and anteverted nostrils), laryngeal cleft, hypospadias, cryptorchidism, and psychomotor development delay, possibly secondary to birth asphyxia and numerous medical and surgical complications. The mother had a similar facies.

The effect of transforming growth factor-alpha on airway angiogenesis.

A problem in lung transplantation is tracheal or bronchial dehiscence from ischemia. To determine if an angiogenic factor applied to the airway would improve capillary regrowth, a three-ring segment of trachea was completely severed and sutured in rats. In one group of animals the ischemic segment was wrapped with Gelfoam soaked in an angiogenic factor, transforming growth factor-alpha. In a second group the ischemic area was wrapped with Gelfoam soaked with only the vehicle. In a third group the devascularized area received no additional treatment. One animal from each group was killed daily for 7 days after operation. The tracheal vasculature was cast and viewed by light and scanning electron microscopy. None of the four animals that died early were in the transforming growth factor-alpha group. All animals lost weight between the day of operation and death, but this was least in the transforming growth factor-alpha group (p = 0.05). The light microscopy showed ischemic changes and the development of granulation tissue. The scanning electron microscopy of the vascular casts showed extensive loss of the vessels in the cut area. On day 1 the vessels of all animals dilated and their walls became rough. By day 3 a few corkscrew vessels penetrated the ischemic zone. By day 4 the animal that received transforming growth factor-alpha had more capillaries than the others. By day 6 revascularization in the transforming growth factor-alpha animal was abundant. Besides budding, new capillaries appeared to develop by lateral growth. After the fifth day vessels about 30 to 50 microns in diameter bulged focally. On the bulges, ridges the size, shape, and pattern of capillaries formed. Capillary formation in this manner has not been reported previously. Revascularization emerged sooner and more extensively with transforming growth factor-alpha. No adverse effect of transforming growth factor-alpha was found.

Endobronchial lipoma.

An endobronchial lipoma has been studied with light, scanning, and transmission electron microscopes, and the literature has been reviewed. Endobronchial lipoma is a type of hamartoma unique only in terms of its specific adult-type fat cell and its location. Of 49 endobronchial lipomas, eight have been reported in obese persons. The neoplasm appears to propagate at its peripheral zone through continuous incorporation and fusion of globules of fat in the spindle-shaped precursor cells. Although benign pulmonary tumors make up about 3 percent and endobronchial lipomas only about 0.1 percent of all pulmonary tumors, benign endobronchial tumors may cause unnecessary morbidity and mortality if not properly managed.

The tuberculosis clinic.

Patient compliance is the major obstacle to successful treatment of tuberculosis. To counter factors of inconstant attention to compliance, inconsistent follow-up, and incomplete documentation, a tuberculosis clinic, managed by nurse specialists, was established. To evaluate this clinic, records of all patients with tuberculosis followed-up there were compared with patients with tuberculosis observed in the other clinics over a nine-year period. Twelve percent of patients in the general clinics group had complete, documented, effective treatment compared with 86 percent in the tuberculosis clinic group. Only 31 percent of the general clinics patients compared with 100 percent of the tuberculosis clinic patients had completely documented follow-up. In hospitals in endemic areas for tuberculosis, a tuberculosis clinic may be superior to general clinics for the care of patients with tuberculosis. Staff of a specialized clinic can quickly identify a break in therapy, provide support necessary for better compliance, lessen the number of incomplete records, and decrease the number of patients who do not receive full therapy.

Endothelin-1 focally constricts pulmonary veins in rats.

Serum endothelin levels increase during sepsis, ischemia, reperfusion, pulmonary operations, and systemic hypertension after surgery. Despite extensive study, the site and extent of action of endothelin on the pulmonary microcirculation are not well established. To assess the effect of endothelin on the pulmonary vasculature, especially the veins, the circulation of the lung was cast with methyl methacrylate 10 minutes after endothelin-1 was given intravenously to rats. Endothelin-1, at concentrations of 0.1, 1.0, and 10.0 micrograms/kg of body weight, increased the mean systemic arterial blood pressure 8%, 7%, and 17% (p < 0.01) and mean pulmonary arterial blood pressure 15%, 28%, and 53%, respectively (p < 0.01). The proportional increases in the pulmonary pressures were greater than those of the systemic pressures (p < 0.01). Scanning electron microscopy of cast blood vessels showed more contraction of the veins than the arteries. For doses of 0, 0.1, 1.0, and 10.0 micrograms/kg, the respective focal contraction of small veins was 6.7% (+/- 4.4), 15.4% (+/- 9.1), 23.3% (+/- 10.1), and 14.4% (+/- 9.0) of the vessel diameter (p < 0.01). In addition, the diameter of capillaries increased (p < 0.01) and the capillary interspaces decreased (p < 0.01) after endothelin administration, but not in a linear dose-dependent manner. The dose of endothelin correlated with the change in the mean systemic (r = 0.82, p < 0.01) and the mean pulmonary (r = 0.80, p < 0.01) blood pressures. The mean pulmonary pressure change correlated with the focal venous contraction on the casts (r = 0.35, p < 0.01), capillary diameter (r = 0.64, p < 0.01), and capillary interspace distance (r = -0.34, p < 0.01). The venous contraction was related to the capillary diameter (r = 0.26, p < 0.01). The most notable effect of endothelin-1 in rat pulmonary microcirculation is focal constriction of small veins. Because this effect may lead to pulmonary edema, endothelin antagonists may be of benefit in a variety of clinical situations.

Testing for isoniazid. An evaluation of the Arkansas method.

To better treat and eliminate tuberculosis, patient compliance must be improved. Compliance can be evaluated by measuring a drug or its metabolite in the urine. In Arkansas, a simple colorimetric method of checking the urine for isoniazid (the Potts-Cozart test) has been used for many years, but it is relatively unknown outside that state and its reliability has not been confirmed. To evaluate this test, urine was blindly tested from patients from a tuberculosis clinic. Controls included urine from patients from a substance abuse clinic and Veterans Medical Center. In more than 200 urine samples tested, no false-positives were found. Urinalysis showed normal values for three patients who were supposed to be receiving antituberculosis medication, but it is likely that these patients were noncompliant. A peculiarity of the test was that the color change with positive tests varied. To investigate this variation, absorption spectroscopy of many substances was performed. Nicotine accounted for the different shade of blue associated with the positive test, but the color produced and the absorption spectroscopy were different from isoniazid, so it did not confuse the interpretation of the results. This test for isoniazid in the urine is simple, quick, inexpensive, easy to interpret, and reliable. It also can be used to detect nicotine and its metabolites.

Factors associated with pulmonary infarction. A discriminant analysis study.

To determine the relative importance of multiple interrelated factors that have been considered to contribute to pulmonary infarction, the authors performed a discriminant analysis on consecutively autopsied patients with pulmonary embolism. From the clinic records of 45 individuals, the authors tabulated the underlying illness, history of valvular or ischemic heart disease, right and left ventricular failure, sepsis, shock, malignancy, premortem functional status, and the clinician's suspicion of pulmonary embolism. At postmortem examination, the authors measured and recorded the extent of emphysema, pneumonia, neoplasia, pulmonary vascular atherosclerosis; thickness and dilatation of both cardiac ventricles; the presence of valvular heart disease; the number, diameter, and amount of occlusion of the pulmonary arteries that contained thromboemboli; the extension of the clot, the size of the infarct; the Reid-Index; and the thickness of pulmonary and bronchial arterial wall. The major determinants of infarction were as follows: poor premortem functional status, the number of lobes having emboli, left ventricular failure, and the presence of lung cancer. The authors then tested the equation generated from these patients on 21 additional patients. The discriminant function correctly classified 81% of first group and predicted the occurrence of infarction in new patients with 70% accuracy. The size of the infarct was most correlated with the use of vasodilators and the embolic burden.

A coded study of antitumor immunity to human lung cancer assayed by tube leukocyte adherence inhibition.

The present study was undertaken to evaluate the specificity of antitumor immunity to human lung cancer, measured by an in vitro assay--tube leukocyte adherence inhibition (LAI). We standardized and monitored the putative tumor antigen activity of the extracts by testing leukocytes from controls and patients with lung cancer in the Montreal General Hospital. A specific antitumor response to a lung cancer antigen was detected with coded leukocytes from 56% (20 out of 36) of patients with epidermoid lung cancer. By contrast, 4% (2 out of 53) of patients with inflammatory lung disease and none of 46 other patients with cancer metastatic to the lung or with other diagnoses had an LAI-positive result. The LAI response was inversely related to the extent of cancer: 80% (8 of 10) with Stage I, 66% (2 of 3) with Stage II, 54% (6 of 11) with localized Stage III, and 33% (4 of 12) with widespread Stage III were LAI positive. Leukocytes from patients with epidermoid, adenocarcinoma, or small cell lung cancer reacted to a common tumor antigen shared by extracts of epidermoid and small cell lung cancer. This study with coded samples from a remote hospital confirms the results of other investigators that the LAI measures an antitumor immune response to human organ-specific neoantigens.

Tuberculosis treatment for the beginning of the next century.

As we move into the next century it appears that new antituberculosis drugs will arise from four categories: 1) new use of old drugs, 2) new delivery of old drugs, 3) new drugs within old classes, and 4) new classes of drugs. Old drugs such as clofazimine and its analogues, rifabutin, the macrolides, aminoglycosides, quinolones and perhaps vitamin D may find a way into better regimens. New therapy may also arise from new combinations and new uses of current antituberculosis drugs. New drugs are being developed in the rifamycin, fluoroquinolone, and nitroimidazole families. Several immune amplifiers, such as interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and interleukin-12 (IL-12) have undergone pilot testing. Counteracting adhesion molecules is being tested for several infectious diseases. With the unraveling of the tuberculosis genome, attacking enzymes unique to Mycobacterium tuberculosis is easier and allows us to hit elements in both a metabolic pathway and its alternate pathway. Interfering with transcription factors that bind DNA but do not promote RNA production could interrupt transcription. Genetic products of mycobacteria can be modified to cause their own death. Phages may deliver antisense nucleic acids for inhibition of mycobacterial gene expression. The distinction between drugs, immunotherapies and vaccines may blur.

Structural and pathologic changes in the lung vasculature in chronic liver disease.

The hepatopulmonary syndrome results from erythrocytes bypassing the lung without oxygenation. In addition to ventilation-perfusion mismatching, the hypoxemia may result from portapulmonary shunting, passage around alveoli through pleural and hilar blood vessels, and intrapulmonary vascular dilatations. Dilated vascular channels between arteries and veins on the pleural surface are seen more often than dilated intrapulmonary capillaries in chronic liver disease. These anastomoses appear grossly as vascular "spider nevi" on the pleura. Portal vein-to-pulmonary vein anastomoses could produce arterial hypoxemia because the deoxygenated portal venous blood can mix with oxygenated pulmonary venous blood. There is an association of esophageal varices with the hepatopulmonary syndrome and anastomoses between the portal veins and pulmonary veins have been found in both animals and humans. As portal pressures increase, the mediastinal veins enlarge, enhancing the chance that they may penetrate the pleura and drain into pulmonary veins. Direct splenic injections in patients, however, suggest that this shunt pathway is uncommon and small. Pulmonary artery injection studies have demonstrated dilated intrapulmonary vascular segments in humans and animals. Dilation of capillaries may allow a more rapid flow through the lung and the greater distance between the erythrocyte and alveolar wall may make it more difficult to oxygenate rapidly passing erythrocytes. Pulmonary capillary dilation can explain the abnormalities of the perfusion lung scan and contrast echocardiogram that portapulmonary shunting cannot. Pulmonary hypertension may occur in chronic liver disease even without arterial hypoxemia, but it is rare. The prevalence of hypertensive pulmonary vascular disease in patients with cirrhosis of the liver is less than 1%, although a higher percentage (2%) has been found when patients with portal hypertension were studied by cardiac catheterization. The hypertensive pulmonary vascular disease (pulmonary arteriopathy with plexiform lesions) that occurs in patients with liver disease appears identical to that encountered in patients with congenital cardiac shunts and unexplained (primary) pulmonary hypertension.

Challenging Alexis Carrel: a study in alternate microvascular techniques.

INTRODUCTION: Alexis Carrel pioneered the full-thickness triangulated vascular repair technique, which led to a Nobel Prize in 1912. However, microvascular anastomotic techniques that do not violate the intima, such as the VCS microclip repair and partial-thickness suturing, limit trauma to the intima, thus minimizing the potential for thrombosis. Our study compares such techniques with the standard full thickness-anastomotic repair. METHODS: Thirty-two end-to-end anastomotic repairs were performed in rat femoral arteries 1 mm or less in diameter. Group I: thirteen full-thickness repairs were completed using 10-0 nylon on a BV75 microm needle. Nineteen extraluminal repairs were performed using either a partial thickness technique with an 11-0 nylon BV50 microm needle (Group II, n = 12) or VCS nonpenetrating clip (Group III, n=7). Casted samples, injected with methylmethacrylate, were harvested at 1 and 3 weeks for histopathological evaluation. The presence of thrombosis, inflammation, endothelialization, angiogenesis and intimal hyperplasia were described for each repair. RESULTS: Statistical analysis revealed no difference between the intraluminal and extraluminal techniques. Patency rates were similar between both groups: 92% (12/13) for Group I and 94% (17/18) for the extraluminal Groups II and III combined. One-hundred per cent of partial thickness suture repairs were patent. Histology revealed localized inflammation to the adventitia and media, as well as endothelialization at 1 week for anastomoses in Groups II and III. The intima of Group I demonstrated proliferative characteristics in contrast to the extraluminal groups, where secretory myofibroblasts were prevalent. The anastomotic microcirculation did not originate from the repaired artery in any of the groups. CONCLUSION: Patency rates with end-to-end anastomotic repairs using a partial thickness technique are comparable to the standard full-thickness technique. Repairs that do not include the intima revealed focal inflammatory responses to the outer layers and more rapid endothelialization, while neighboring vessels perfuse the healing anastomosis.

Silver staining of Pneumocystis carinii in the rat's lung.

The backscattered electron imaging mode of the scanning electron microscope was used to study the ontogenetic acquisition of argyrophilia in Pneumocystis carinii in rats. Silver staining continually increased from the late trophozoite to the mature cyst stage. The silver uptake began with a fine outline at the surface of the bodies of the late trophozoites; their cellular extensions, however, did not stain. The oblate precyst forms acquired the silver in heterogeneous patches. On spherical cysts the silver staining became more uniform and intense with at least one dense spot. The spherical and collapsed cysts also had short silver staining projections that may represent microvilli. Collapsed forms were paler than spherical ones and appear to be cysts that have undergone partial or complete release of sporozoites. These cell surface observations confirm and amplify previous transmission electron microscopical and histochemical studies indicating that silver staining correlates with the acquisition of the cell pellicle.

Endothelin-1 causes luminal constrictions in rat cochlear veins.

Serum levels of the vasoconstrictor endothelin-1 (ET-1) increase in ischemia and systemic hypertension. We examined the effects of ET-1 on the cochlear microvasculature. Blood vessels were cast with methacrylate in adult male Wistar Kyoto rats, 10 min after intravenous injection of ET-1 (1.0 microg/kg); control animals received saline. Systemic blood pressure was recorded continuously. ET-1 increased the average systolic pressure by 18% and average diastolic pressure by 22% (P < 0.01). Scanning electron microscopy of cast vessels showed multiple circumscribed luminal constrictions on: (1) postcapillary venules; (2) collecting veins; (3) where collecting veins merged with the spiral modiolar vein; (4) on the spiral modiolar vein itself. Circumscribed constrictions in arteries were not observed. In ET-1 injected animals focal contractions of collecting veins reduced luminal width by 13.4% +/- 2.9 (P < 0.01). In control rats, constrictions on venous casts were minimal and constrictions on arteries were not observed. The present study shows that ET-1 is involved in local control of cochlear blood flow in that it focally contracts cochlear veins. It is suggested that this might be due to the high affinity of ET-1 receptors and/or the large number of ET-1 receptors on contractile cells in venous walls.

Pulmonary lymphatic filling is increased in spontaneously hypertensive rats.

Extravascular lung liquid must rely on tissue-space pressure gradients to drive it into the lymphatics because the fluid is outside the lymphatic contractile pumping and valve control. Focal tissue pressure changes could result from muscular contraction in the blood vessel walls. Perivascular lymphatics usually lie within the adventitia of pulmonary blood vessels, and are generally more noticeable in veins than arteries. Spontaneously hypertensive rats have exaggerated focal pulmonary venous muscle (venous sphincters). These muscular tufts are often near initial lymphatics; if their contraction was important for lymph transport, spontaneously hypertensive rats could have more lymphatic filling in the areas of the pulmonary venous sphincters than normotensive rats. Because the focal muscularity is found in pulmonary veins more than arteries, veins may have more focal lymphatic filling than arteries. To test these hypotheses, lung histology and vascular and lymphatic casts of spontaneously hypertensive and normotensive rats were examined. Contracted venous sphincters were found on 108 of 127 veins with lymphatics in the spontaneously hypertensive rats and 5 of 41 in the normotensive rats P<0.01). The spontaneously hypertensive rats had deeper venous contractions and more lymphatic filling around both arteries and veins (P<0.01). In the hypertensive rats, the venous was greater than the arterial lymphatic filling (P<0.01). On the pleural surface, hypertensive rats also had greater lymphatic filling than controls (P<0.01). This anatomic evidence suggests that pulmonary venous sphincters are associated with focal lymphatic filling, and perivascular muscle action might be a component of the pulmonary lymphatic system.

Treatment of tuberculosis in a nurse-managed clinic.

From July 1982 to January 1986, we saw 86 patients in the tuberculosis clinic; 77 (90%) were alcoholics; all were males, 71 (83%) were black, 14 (16%) were white, and one (1%) was hispanic. Of these, 10 patients (12%) failed to complete therapy and were referred to the Chicago Board of Health. Nine patients (10%) were dropped from the clinic: three moved from the state of Illinois, three died of nontuberculosis causes, and three were transferred to the Chest Clinic for other medical problems. Therefore, 67 patients (78%) successfully completed therapy. Our high rate of success is attributed to constant, high-intensity contact and consistent supervision of these potentially noncompliant patients.