Arterial-jugular vein free amino acid levels in patients with head injuries: important role of glutamine in cerebral nitrogen metabolism

Traumatic brain injury is the single largest contributor of trauma center deaths. Injury to the brain cannot be considered as an isolated event, affecting only this organ. Profound hypoglutaminemia commonly seen in patients with head injuries may be caused by the diminished release of glutamine from the brain to the systemic circulation. To assess this hypothesis, we have simultaneously measured the free amino acid (AA) levels in systemic arterial (A, radial artery), cerebral venous (JV, jugular bulb), and systemic venous (PA, pulmonary artery) plasma in 11 adult patients with severe head injuries once within 48 hours of the initial injury before starting nutritional support and again after 3 to 4 days of enteral feeding. Cerebral organ (A-JV) changes of AA levels were compared with whole body systemic (A-PA) changes. Arterial total AA levels when compared with reported normal values are diminished by 46% in patients with isolated severe injuries. Cerebral outflow of glutamine is 6% of the total AA output compared with 73% in normals. The systemic outflow of glutamine in patients with brain injuries is 28% of total AA flow. Despite this high systemic output, significant hypoglutaminemia persists. Feeding for 3 days did not appreciably change the arterial plasma AA levels except that of glutamate and citrulline. A significant (p = 0.01) linear relationship between glutamine (product) and glutamate (precursor) was seen in JV samples but not in A or PA samples. The ratio of plasma glutamine to glutamate was decreased significantly only in JV during nutritional support, and this was caused mainly by an increase in glutamate levels. This may be owing to defective amidation to glutamine, inasmuch as gamma aminobutyric acid (GABA) levels were only minimally affected. Nutritional support improves the net release of glutamine from the brain. This suggests that supplementing the diet with glutamine may be beneficial to support systemic requirements in patients with severe head injuries.     

Mannan antigenemia in the diagnosis of invasive Candida infections

Because it is often difficult to diagnose invasive Candida infections, a sensitive hemagglutination inhibition assay to detect the surface antigen, mannan, was developed. Mannan antigenemia was detected early in the course of infection in 4 of 14 patients with systemic candidiasis and 2 of 5 patients with invasive gastrointestinal candidiasis. Mannan was not detected in 48 patients with noninvasive Candida or other systemic mycotic infections or in 99% of 234 patients in other control groups. Mannan antibodies were almost universally present in both candidiasis and control groups. In four patients with systemic candidiasis, an early period of mannan antigenemia was followed by a rapid rise in mannan antibody titer. These findings suggest that antemortem diagnosis would be improved in one-third of cases of invasive Candida infection detected by the hemagglutination inhibition assay. A positive test for serum mannan would be an early and specific signal of invasive disease.     

Overcoming right ventricular failure with left ventricular assist devices

BACKGROUND: Right ventricular failure can lead to circulatory collapse while on left ventricular assist device support. By shunting blood from the femoral vein to the left ventricular assist device, cardiac output can be increased, but arterial oxygen saturation will decrease. METHODS: To determine the effects on O2 delivery, a model was developed on the basis of O2 uptake in the lungs and whole body O2 consumption. An equation was derived that related cardiac output, pulmonary venous O2 saturation, O2 consumption, and the ratio of shunt-to-systemic blood flow to systemic O2 delivery. RESULTS: When total cardiac output increases, the shunt will increase systemic O2 delivery while decreasing arterial O2 saturation and leaving systemic venous O2 saturation unaltered. When total output does not increase, the shunt will decrease systemic O2 delivery, arterial O2 saturation, and systemic venous O2 saturation. CONCLUSIONS: The analysis suggests that measuring systemic venous oxygen saturation may be a useful way to monitor patient safety. A decrease in systemic venous O2 saturation when creating the shunt implies an inadequate increase in cardiac output.     

Advances in palliative care for the patient with scleroderma

Few studies published within the past year have addressed palliative care for the patient with scleroderma or systemic sclerosis. However, progress continues to be made, and important contributions have been made with respect to different vasodilator preparations for Raynaud's phenomenon, a possible role for diltiazem in the treatment of calcinosis, and the treatment of gut dysmotility. A number of comprehensive review papers on different aspects of management, mainly organ based, were included in the recently published textbook Systemic Sclerosis. Until there is an effective disease-modifying treatment for systemic sclerosis, management will be largely palliative and is best delivered by a multidisciplinary team.     

Bulky centroblastic non-Hodgkin's lymphoma of the cranium vault mimicking brain involvement managed with chemotherapy: a case report

BACKGROUND: Patients with central nervous system (CNS) involvement by high grade non-Hodgkin's lymphoma (NHL) have a poor prognosis. The roles of computed tomography, radiotherapy, and intrathecal and systemic chemotherapy still need to be defined. METHODS: A patient with bulky cranial lymphoma mimicking brain involvement is reported. A 62-year-old man was admitted with a huge scalp lump, headache, fatigue, and focal and generalized neurologic symptoms. Computed tomography showed an abnormal mass in the frontoparietal region involving the subcutaneous scalp, osteolytic destruction of the cranial vault, and a bulky mass that was interpreted to be intracranial. A systemic survey also revealed bulky retroperitoneal involvement and focal involvement of the spleen. Biopsy revealed a B-cell NHL of centroblastic type according to the Kiel classification. RESULTS: The patient was treated with a modified combination of cyclophosphamide plus mitoxantrone plus vincristine plus prednisone (CNOP) and intrathecal methotrexate. The patient responded with complete remission, including partial bone restoration of the cranium. At the time of this writing, his relapse free survival lasted 5 years. CONCLUSIONS: The initial interpretation of this case indicated that systemic chemotherapy with modified CNOP plus intrathecal methotrexate would be useful in the management of NHL with CNS involvement. The clinical outcome with rapid neurologic repair and also bone restoration of the cranial vault within 5 years suggests that the lymphoma probably never penetrated the dura and a successful treatment was achieved with combination chemotherapy only.     

Systems approach to the development of equipment provision for roentgenological research]

A systemic approach to the X-ray out fits allowed 3 levels of the roentgen-diagnostic process to be singled out, viz. the lower with the data the data "normally--anormality", the medium, with a tentative conclusion and the highest, with an authentic diagnosis at the output end. The levels may be characterized by formulas reflecting the number of inputs, processes (methods) and outputs. The optimal roentgenological facilities should be in keeping with the diagnostic levels formulas. The prospects for improving the facilities involve a systemic approach to the development of equipment and an integration on this basis of the investigation methods, both horizontally (within the framework of roentgenology) and vertically (outside roentgenology).     

Atrial conduction abnormalities in patients with systemic progressive sclerosis

BACKGROUND: Atrial abnormalities in patients with progressive systemic sclerosis have not been evaluated in terms of intra-atrial conduction. We hypothesized that a delay in atrial conduction in these patients might produce diastolic abnormalities as well as atrial arrhythmias. OBJECTIVE: To evaluate the atrial function of patients with progressive systemic sclerosis by using echocardiography to measure the intra-atrial electromechanical activation coupling interval. METHODS: Twenty patients with progressive systemic sclerosis were assessed by Doppler echocardiography. Twenty age-matched healthy controls were also evaluated. Two-dimensional guided M-modes of ventricular long axes were recorded using simultaneous phono- and electrocardiograms of the apical four chamber view at the right lateral, septal and left lateral sites of the atrioventricular rings. Transmitral and tricuspid pulsed Doppler flow velocities were also recorded. Filtered P wave duration was measured on the signal averaged ECG to determine the duration of atrial electrical activation. RESULTS: There was a delay in P on the electrocardiogram (P) at the onset of atrial contraction on long axis M-modes at all three atrioventricular ring sites in patients with progressive systemic sclerosis as compared with controls (P-right; 56 +/- 13 vs 47 +/- 10 ms, P-septal; 74 +/- 14 vs 55 +/- 10 ms, and P-lateral; 93 +/- 16 vs 72 +/- 11 ms, P < 0.01). Inter-atrial conduction time [(P-lateral)-(P-right)] was delayed in patients with progressive systemic sclerosis, compared with healthy controls (37 +/- 15 vs 25 +/- 6 ms, P < 0.01). Mitral A waves acceleration and deceleration times were also decreased in the patients. The interval was prolonged between P to the onset and the peak of the A wave in transmitral flow. Duration of the filtered P wave was significantly prolonged in progressive systemic sclerosis as compared with controls (124 +/- 12 ms vs 106 +/- 8 ms, P < 0.01). PQ intervals, E waves and acceleration and deceleration times did not differ significantly in progressive systemic sclerosis vs, controls. The A wave acceleration rate on transmitral flow (peak A wave velocity/acceleration time) showed a significant correlation with inter-atrial conduction delay (r = 0.55, P < 0.01). CONCLUSIONS: Intra-atrial electromechanical coupling intervals were delayed in patients with progressive systemic sclerosis. Thus, the mechanical late diastolic filling time due to atrial contraction in the total diastolic phase was severely limited, and this resulted in a restricted mitral A wave. We should therefore evaluate patients with progressive systemic sclerosis for significant atrial abnormalities.     

Aureobasidium pneumonia in a post liver transplant recipient: a case report

This is the first report of Aureobasidium (A.) pullulans as an opportunistic pulmonary infection in a liver transplant recipient. A 46-year-old caucasian man had an orthotopic liver transplant in 1988. His liver disease was primary sclerosing cholangitis. He required 2 subsequent liver re-transplants for primary graft non-function and acute rejection. The patient had been living in the California desert for two months prior to admission and presented with ventilator-dependent acute respiratory failure and hemodialysis-dependent acute renal failure. Imaging studies revealed severe bilateral infiltrates. His initial bronchoalveolar lavage (BAL) and brushings grew A. pullulans. Pancultures, including sputum and throat cultures, were negative for bacterial or other fungal organisms. The patient responded to pulmonary support and aggressive systemic antifungal agents while being maintained on cyclosporine and prednisone for immunosuppression. He was discharged to a skilled nursing facility 37 days after hospitalisation. Delay in discharge was primarily due to severe malnutrition and renal impairment. Opportunistic fungal infections continue to be a major problem in immunosuppressed patients including liver transplant recipients. Here we report a pulmonary infection with Coccidioides (C.) immitis and superinfection with A. pullulans. Opportunistic infections such as A. pullulans can be treated successfully with systemic fluconazole when amphotericin B is not well tolerated.     

Inferior vena cava filter used for unresectable renal cell carcinoma with tumor thrombi

A titanium Greenfield inferior vena cava filter was used for the treatment of 2 patients with unresectable renal cell carcinomas with tumor thrombi to prevent a fatal pulmonary embolism induced by tumor clots released during systemic interferon therapy and embolization of the primary tumor. After treatment, the size of the renal cell carcinomas at the primary site and the tumor thrombi decreased by 50%. There were no fatal pulmonary embolisms or complications related to the filter during the observation period (24 and 25 months) after therapy. This method may be useful in the prevention of a fatal pulmonary embolism induced by embolization and systemic interferon therapy in these patients.     

Cerebral venous sinus thrombosis associated with systemic multiple hemangiomas manifesting as chronic subdural hematoma--case report

A 35-year-old male was admitted with headache, nausea, and vomiting persisting for 2 days. Computed tomography (CT) revealed a left chronic subdural hematoma. Cerebral angiography demonstrated cerebral venous sinus thrombosis (CVST). He had presented with a subcutaneous mass involving the neck at age 2 years, which was shown to be a cavernous angioma, and thereafter shown signs of consumptive coagulopathy with systemic multiple hemangiomas. Burr hole aspiration of the hematoma was performed. Seventy-two-hours later, he developed clouding of consciousness and right hemiparesis. CT revealed a fresh hematoma in the operated subdural cavity and hemorrhagic diathesis manifested. A frontotemporoparietal large craniotomy was performed to remove the hematoma. Extensive electrocauterization was required. He had a satisfactory postoperative course. Collateral venous pathways, resulting from the CVST due to systemic multiple hemangiomas, may have caused hemodynamic stress in the bridging veins which subsequently induced chronic subdural hematoma.     

Relationship between abnormalities on high-resolution CT and pulmonary function in systemic sclerosis

STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.     

Therapeutic periocular vaccination with a subunit vaccine induces higher levels of herpes simplex virus-specific tear secretory immunoglobulin A than systemic vaccination and provides protection against recurrent spontaneous ocular shedding of virus in latently infected rabbits

Rabbits latently infected with herpes simplex virus type 1 (HSV-1) were vaccinated either periocularly or systemically with a subunit vaccine (gB2 + gD2) plus adjuvant or adjuvant alone. Tear films were collected daily to measure recurrent infectious HSV-1 shedding. After systemic vaccination, the latently infected rabbits were not protected against recurrent ocular viral shedding (HSV-1-positive tear film cultures/total cultures) compared with either the systemic or periocular adjuvant controls (systemic vaccination = 49 of 972, 5.0%; systemic control = 46 of 972, 4.7%; periocular control = 43 of 930, 4.6%; P > 0.8). In contrast, latently infected rabbits vaccinated periocularly with the same vaccine had significantly reduced recurrent shedding (20 of 1026, 2.0%) compared with controls (P < 0.001) or systemic vaccination (P = 0.0002). Thus, recurrent HSV-1 shedding was significantly reduced by therapeutic local periocular subunit vaccination but not by therapeutic systemic subunit vaccination. Neutralizing antibody titers in the serum of systemically and ocularly vaccinated rabbits was similar. In contrast, HSV-specific tear secretory immunoglobulin A was significantly higher in the ocularly vaccinated group (P < 0.01). These results strongly suggest that in the rabbit, and presumably in humans, the local ocular (mucosal) immune response is much more important than the systemic immune response for therapeutic protection against recurrent ocular HSV-1. Thus development of a therapeutic vaccine against recurrent ocular HSV-1 should be directed at enhancing the local ocular (mucosal) immune response.     

Myopathy in primary systemic amyloidosis

OBJECTIVE: To define the natural history of primary systemic amyloidosis when muscle involvement is prominent at presentation. METHODS: A retrospective review was carried out of all patients seen at the tertiary referral practice of the Mayo Clinic between 1 January 1960 and 31 December 1994. All patients with primary systemic amyloidosis and proof of amyloid deposits by muscle biopsy were included for analysis. No patients were lost to follow up. RESULTS: Twelve patients were identified with amyloidosis in muscle. Muscle involvement was the most prominent symptom in patients who had widespread visceral involvement, which included the heart, peripheral nerve, and tongue. Of the 12, three had skeletal muscle pseudohypertrophy. All patients had a demonstrable dysproteinaemia by the finding of free light chain in the serum or urine, a discrete monoclonal peak on serum or urine protein electrophoresis, or a monoclonal population of plasma cells in the bone marrow. Measurement of creatine kinase was not a useful test. Of eight patients treated with chemotherapy based on alkylating agents, three responded. The median survival for the entire group was 12 months. CONCLUSIONS: The finding of a monoclonal protein in a patient with muscle weakness is an important clue to the diagnosis of primary systemic amyloidosis. Most patients have visceral involvement outside the musculoskeletal system. A subset of patients seems to respond to systemic chemotherapy. The overall survival, however, remains poor, with most patients dying of cardiac failure. Immunoelectrophoresis of serum and urine should be a routine diagnostic test during the evaluation of myopathy of unknown cause.     

An unusual case of primary leptomeningeal marginal zone B-cell lymphoma

Primary leptomeningeal lymphomas are rare, and usually follow a rapid clinical course with early systemic involvement. A 60-year-old woman presented with a 3-year history of worsening seizures and memory loss. Neuroimaging showed widespread meningeal calcification. After extensive investigations a meningeal biopsy revealed a low-grade B-cell lymphoma categorized as an extranodal marginal zone B-cell lymphoma, attributed to the same histological group as the MALT (mucosa-associated lymphoid tissue) lymphomas described in the stomach, thyroid, salivary glands and orbit. There was no evidence of systemic involvement. The extensive meningeal calcification would appear to be a novel finding in primary leptomeningeal lymphoma whereas the unusually long clinical history in this case is possibly related to the particular histological type of low-grade B-cell lymphoma.     

Hemoptysis in a patient with acquired anomaly of the arterial vascularization of the lung

An anomalous systemic pulmonary supply may be acquired and present only one symptom: hemoptysis. The incidence of this pathology is unknown. A case of acquired systemic pulmonary arterialization was observed after surgical intervention of myocardium vascularization with the left mammary artery. The diagnosis was obtained through an arteriography of the left mammary artery. In this case, the therapy consists in ablating the affected parenchyma followed by the interposition of a bovine pericardium patch between the mammary artery and the remaining pulmonary tissue.     

Widespread tinea corporis in an immunocompetent patient resistant to all conventional forms of treatment

A 70-year-old immunocompetent man with a more than forty-year history of tinea corporis unresponsive to multiple systemic and topical antifungal agents, including systemic terbinafine, is described. The literature with respect to persistent dermatophyte infection is reviewed.     

CD34+-enriched donor lymphocyte infusions in a case of pure red cell aplasia and late graft failure after major ABO-incompatible bone marrow transplantation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Increased life expectancy will result in a higher prevalence of AF. Treatment of AF constitutes a persistent medical dilemma. Different multicenter trials have confirmed that oral anticoagulant therapy is the best choice for the prevention of systemic embolism. It must be recognized, however, that the incidence of systemic embolism in patients with AF varies according to the presence and type of underlying heart disease. Advanced age increases the risk of emboli in patients with AF. At the same time, older patients have a higher risk of hemorrhage when treated with oral anticoagulants. Thus, careful titrated individual oral anticoagulant therapy targeted to a safe and effective INR must be considered in patients with AF. Another dilemma in AF patients is the convenience of restoring sinus rhythm and indicating permanent antiarrhythmic therapy versus the alternative of heart rate control plus oral anticoagulants. Several multicenter trials now in progress have addressed this issue and most likely will answer these questions. Identification of patients with paroxysmal AF and risk of systemic embolism constitutes another dilemma, since only a small proportion of these patients evolve to chronic arrhythmia. Advanced age, history of hypertension and left atrial enlargement in 2D Echo are well recognized risk factors for embolism in patients with non valvular paroxysmal AF. A history of previous embolism constitutes another risk factor and supports the hypothesis that AF may activate systemic coagulation factors and left atrial thrombus formation in some patients.     

Technique and rationale of lymph node dissection in bronchial carcinoma

BACKGROUND: Psoriasis is a chronic T-cell-mediated inflammatory skin disease which can be treated with topical medication, phototherapy or systemic medication. A subgroup of psoriatic patients does not respond to monotherapy and needs combination therapy. We used low-dose narrow-band UVB phototherapy, combined with balneotherapy, short-contact anthralin, liquor carbonis detergens and calcipotriol for treatment of psoriatic patients in our day care centre. OBJECTIVE: Our purpose was to study the efficacy, induction of erythema and effect on systemic T-cell activation of this combination therapy. METHODS: Skin reflectance spectrophotometry was used to measure skin erythema. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic patients. Serum soluble IL-2 receptor (sIL2-R) levels were measured by an ELISA. RESULTS: The possible erythematogenic effect of low-dose narrow-band UVB irradiation was studied (skin reflectance spectrophotometer) in a control group of psoriatic patients (n = 11). No induction of skin erythema was seen. Subsequently, this low-dose irradiation regimen was used in combination with topical medication in 26 psoriatic patients. A 90% decrease in the PASI was seen after a mean number of 35 treatment sessions. Seventeen patients (65%) remained in remission during the following 6 months. Serum sIL-2R levels were elevated in all patients (mean 913 U/ml) and did not change during treatment. CONCLUSION: Our data indicate that low-dose narrow-band UVB can be used successfully, in combination with topical treatment, in a day care setting to treat psoriatic patients. Since sIL-2R serum levels were not decreased, it can be speculated that this treatment does not induce systemic immunosuppression.     

Ocular and sinus microsporidial infection cured with systemic albendazole

PURPOSE: To report treatment of a patient with acquired immunodeficiency syndrome (AIDS) and ocular and paranasal sinus microsporidial infection. METHOD: Case report. RESULTS: A patient with AIDS and ocular microsporidial infection experienced resolution of ocular symptoms with topical fumagillin, but symptoms recurred upon cessation of therapy. Paranasal sinus microsporidial infection was diagnosed. The patient received sequential systemic treatment with itraconazole followed by albendazole. Sinus symptoms resolved with albendazole. He remained symptom-free with a normal examination 17 months after concluding therapy. CONCLUSIONS: Although fumagillin and itraconazole may have played a role, systemic albendazole appears to be responsible for clinical resolution of microsporidial infection.     

CT angiogram sign: incidence and significance in lobar consolidations evaluated by contrast-enhanced CT

BACKGROUND: Neuropathological data are very scarce in systemic sclerosis and fail to demonstrate primary changes in the brains of such patients. CASE DESCRIPTIONS: A 41-year-old woman with CREST syndrome developed signs of dementia after an episode of severe dehydration and died two months later of septic shock. A 63-year-old woman with CREST syndrome and a history of two unexplained transient ischemic attacks had had balance disorders since age 62. She died of severe pulmonary hypertension. In both cases, the autopsy showed extensive wall calcification of small arteries and arterioles in the brain, primarily in the basal ganglia, and also in the frontal lobes and the cerebellar area in the second case. No known cause of cerebrovascular calcification was found in either patient. CONCLUSION: The neuropathological findings in these two patients suggest that systemic sclerosis may induce primary vascular changes in the brain, of which calcification may be a marker.