Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study.

BACKGROUND: There is much controversy about the ideal approach to the management of community acquired pneumonia (CAP). Recommendations differ from a pathogen directed approach to an empirical strategy with broad spectrum antibiotics. METHODS: In a prospective randomised open study performed between 1998 and 2000, a pathogen directed treatment (PDT) approach was compared with an empirical broad spectrum antibiotic treatment (EAT) strategy according to the ATS guidelines of 1993 in 262 hospitalised patients with CAP. Clinical efficacy was primarily determined by the length of hospital stay (LOS). Secondary outcome parameters for clinical efficacy were assessment of therapeutic failure on antibiotics, 30 day mortality, duration of antibiotic treatment, resolution of fever, side effects, and quality of life. RESULTS: Three hundred and three patients were enrolled in the study; 41 were excluded, leaving 262 with results available for analysis. No significant differences were found between the two treatment groups in LOS, 30 day mortality, clinical failure, or resolution of fever. Side effects, although they did not have a significant influence on the outcome parameters, occurred more frequently in patients in the EAT group than in those in the PDT group (60% v 17%, 95% CI -0.5 to -0.3; p<0.001). CONCLUSIONS: An EAT strategy with broad spectrum antibiotics for the management of hospitalised patients with CAP has comparable clinical efficacy to a PDT approach.

Prospective evaluation of pneumonia severity index in hospitalised patients with community-acquired pneumonia.

The aim of the present study was to investigate whether the pneumonia severity index (PSI) could adequately predict the severity of community-acquired pneumonia (CAP) and could be used as a severity of illness classification system. Furthermore, reasons that may influence the decision to admit low risk patients were analysed. In a prospective study 260 patients with CAP were included. Stratification in five risk classes according to the PSI was compared with parameters that are closely related to severity of CAR A significant difference in severity parameters, such as length of stay (P < 0.001) and simplified acute physiologic score and acute physiologic and chronic health evaluation II score (P < 0.001) was found between the five risk classes. Furthermore, a positive British Thoracic Society (BTS) rule and modified BTS rule score was significantly more prevalent in the higher risk classes (P < 0.001). The patient population had an average 30-day mortality of 10% and a mean Intensive Care Unit (ICU) admission rate of 8%. The mortality rate and ICU admission rate significantly differed between the five risk classes (P < 0.001), in which the highest ICU admission rate (40.9%) and the highest mortality percentage (40.9%) were both found in risk class V. Several clinical factors (n = 64), such as an exacerbation of chronic obstructive pulmonary disease in 17 patients and clinical appearance of being ill in 16 patients, lack of improvement on outpatient antibiotic therapy (n = 15) and social circumstances (n = 3) were reasons that influenced the decision to hospitalise low risk patients (n = 82). The results show that the PSI adequately predicted the severity of CAP and can be used as a severity of illness classification in CAP. Clinical and social factors other than those mentioned in the PSI have to be considered when making the decision to hospitalise patients with CAP.

Unusual association of Hodgkin's disease and sarcoidosis.

We report a 51-year-old patient who developed abdominal lymphadenopathy following Hodgkin's disease seven years after she was diagnosed as having sarcoidosis. The patient had been treated with steroids, methotrexate and azathioprine. After three cycles of chemotherapy for Hodgkin's disease, the patient again developed sarcoidosis in the mediastinal lymph nodes. A greater awareness of the co-existence of sarcoidosis and Hodgkin's disease could circumvent the diagnostic difficulties.

Amanita phalloides, a potentially lethal mushroom: its clinical presentation and therapeutic options.

Mushroom poisoning with Amanita phalloides, a rare phenomenon in everyday clinical practice in the Netherlands, must be recognized early in view of its potential morbidity and mortality. In this article 2 cases of amanita intoxication are presented and the pharmacological basis and clinical manifestations discussed. Furthermore, the rationale of various treatment modalities, including the role of liver transplantation, is outlined.

Methylene blue increases myocardial function in septic shock.

OBJECTIVE: To study whether the circulatory changes of human septic shock are mediated in part by nitric oxide. DESIGN: Open-label, nonrandomized clinical trial on the effects of methylene blue, an inhibitor of nitric oxide action. SETTING: Intensive care unit of a teaching hospital. PATIENTS: Nine consecutive patients with documented septic shock and a pulmonary artery catheter in place, after initial resuscitation with fluids, sympathomimetics, and mechanical ventilation. INTERVENTIONS: Hemodynamic and metabolic variables were measured before and then 15, 30, 60, and 120 mins after the start of a 20-min infusion of 2 mg/kg of methylene blue. MEASUREMENTS AND MAIN RESULTS: Patients had a hyperdynamic circulation, and methylene blue increased (p < .01) mean arterial pressure from 84 +/- 18 to 109 +/- 31 mm Hg and cardiac index from 4.7 +/- 0.9 to 5.6 +/- 1.2 L/min/m2, before and 30 mins after starting the methylene blue infusion, respectively. Cardiac filling pressures did not change. In the same time interval, the subnormal systemic vascular resistance index increased (p = .09) and arterial compliance decreased (p < .05). Oxygen delivery and oxygen uptake increased (p < .05) from 714 +/- 188 to 865 +/- 250 mL/min/m2 and from 160 +/- 39 to 186 +/- 44 mL/min/m2, respectively. Except for heart rate, which increased by 11 +/- 8 beats/min (p < .01), variables returned to baseline values at time = 120 mins. CONCLUSIONS: After initial resuscitation from human septic shock, a single dose of methylene blue transiently increases mean arterial pressure and oxygen uptake, associated with a decrease in arterial compliance and increases in myocardial function and oxygen delivery. Hence, nitric oxide may be a mediator of the circulatory changes of human septic shock.

Clinical value of labeled red blood cell scintigraphy in patients with difficult to diagnose gastrointestinal bleeding.

A retrospective study was conducted using 36 patients with gastrointestinal bleeding in whom the diagnosis was not directly apparent from first line diagnostic procedures. Final diagnosis was established by surgery, endoscopy, or postmortem examination in 20 patients. Scintigraphic examination with Tc-99m or In-111 labeled red blood cells yielded 24 positive and 18 negative results. Nine out of 13 positive scans (verified by other diagnostic procedures) accurately identified the site of bleeding. This was considered to be a satisfactory result in this group of difficult to diagnose patients. The lowest success rate was observed in patients taking drugs that interfered with coagulation, or in patients prone to diffuse blood loss because of coagulopathy. Late scans did not offer additional information and the use of In-111 for this purpose was not thought to be of benefit. Although the technique is rather noninvasive and simple, its application should be restricted to selected patients and its interpretation related to the results of other investigations.

Eosinophilic gastroenteritis--a disease with a wide clinical spectrum.

Two patients with eosinophilic gastroenteritis are described. The predominant eosinophilic infiltration of the mucosal layer of the upper gastrointestinal tract resulted in severe protein-losing enteropathy and peripheral eosinophilia in one patient and a malabsorption syndrome due to saccharose and lactose intolerance in another patient. There was a wide range of abdominal symptoms, depending on the site and extent of the disease. The diagnosis was based upon typical biopsy findings. There was a marked lack of any biochemical abnormality. The course of the disease was chronic and relapsing. Symptoms were not controlled with corticosteroids alone; only after the addition of disodium chromoglycate per os was prolonged disease control achieved.

[Hemobilia, a rare and difficult diagnosis]. / Hemobilie, een zeldzame, moeilijke diagnose.

Haemobilia, i.e. blood loss via the bile ducts, is a rare disorder, which may be caused by trauma, vascular disorders, gallstones, infection/inflammation, tumours and coagulation disorders. Haemobilia may cause grave morbidity and mortality. Important symptoms are: gastrointestinal bleeding, jaundice and colicky pains in the right upper abdominal quadrant. Gastroduodenoscopy, ultrasound, ERCP, CT-scan and MRI may be used to obtain additional information when haemobilia is suspected. Selective angiography may provide detailed information of the bleeding, but is less appropriate as an initial screening method. Haemobilia may be treated by selective embolisation of the involved artery or by operative treatment. Embolisation is the treatment of first choice in most situations. We present a case report of a patient with recurrent haemobilia caused by a ruptured aneurysm of a hepatic artery leaking intermittently into the bile ducts. Partly because of the rareness of this syndrome, the disorder was recognized with delay in our patient. After two embolisation attempts had failed, he was treated successfully by obliterative endoaneurysmorrhaphy.

Systemic lupus erythematosus--changing disease patterns in the disease course. Dutch experience with 110 patients studied prospectively.

The aim of this study was to investigate which patients with systemic lupus erythematosus (SLE) are prone to develop more than one exacerbation, and to establish the variability in the clinical symptoms during exacerbations as compared with the initial symptoms of the disease. At disease origin, photosensitivity, pleuritis and Raynaud's phenomenon were slightly increased in the patients with a stable disease, while pericarditis was rarely seen in patients with a remitting disease course. In this prospective study it was clearly shown that during the disease course, depending on the exacerbation frequency, an increasing number of organs were involved. Striking features were the increase in haematological abnormalities in the third exacerbation, and the fact that psychosis and seizures did not recur in the second exacerbation when they were diagnosed in the preceding period. We also showed that symptoms seen in an exacerbation may be quite different from those seen in a previous exacerbation.

Maldistribution of heterogeneous coronary blood flow during canine endotoxin shock.

STUDY OBJECTIVE - The aim was to investigate whether heterogeneous coronary blood flow is maldistributed during endotoxin shock. DESIGN - Variables were studied before (t = 0) and at t = 90 and t = 120 min after bolus injection of saline (n = 6) or endotoxin (n = 6). SUBJECTS - 12 anaesthetised mongrel dogs, weight 20-27 kg, were used. MEASUREMENTS AND MAIN RESULTS - We studied myocardial blood flows in small tissue sections (of about 1 g in left and 2 g in right ventricle) with radioactive microspheres, together with haemodynamic variables and global myocardial metabolism. At t = 0 min in controls, regional flows per 100 g were heterogeneous and ranged from a factor 0.2 to 2.7 and 0.6 to 1.6 of mean flow per 100 g to the left and right ventricle respectively; heterogeneity was unchanged at t = 90 and t = 120 min. Between t = 0, t = 90, and t = 120 min regional flows correlated: r = 0.78(SD 0.14), n = 18, for left ventricle, and r = 0.70(0.17) for right ventricle. In the endotoxin group, cardiac output and mean arterial pressure decreased by 44(7) and 48(11)% respectively, and lactate increased by 3.2(0.6) mmol.litre-1 at t = 120 min. Global left ventricle blood flow and delivery and metabolism of O2 were unchanged; lactate extraction and external work fell. The ratio between global right ventricular O2 delivery and external work also rose. Regional blood flows ranged from a factor 0.2 to 2.7 and 0.1 to 1.8 of mean flow to left and right ventricles respectively; heterogeneity did not differ from controls and did not change with time. Flow correlations with time were reduced: 0.45(0.24) for left ventricle and 0.45(0.26) for right ventricle (both n = 18, p less than 0.005 v controls). The left ventricular endocardial to epicardial flow ratio fell; flow was redistributed to both layers. CONCLUSIONS - Heterogeneous blood flow is redistributed throughout the heart during canine endotoxin shock so that, at unchanged global blood flow and flow heterogeneity, flow decreases in some but increases in other areas. Flow maldistribution may be associated with focal ischaemia, which may be masked by a rise in O2 uptake for a given workload (contractile inefficiency) in overperfused areas, and may thereby contribute to a fall in global myocardial external work for a given O2 delivery.

Systemic lupus erythematosus. III. Observations on clinical renal involvement and follow up of renal function: Dutch experience with 110 patients studied prospectively.

A prospective study of 110 patients with systemic lupus erythematosus (SLE) was undertaken to evaluate the reliability of clinical signs of lupus nephritis, which developed in 39 (35%) patients. Those patients with SLE who showed no clinical signs of lupus nephritis had an excellent survival rate (10 year survival 93%) and retained normal renal function (serum creatinine less than 130 mumols/l); clinical lupus nephritis developed mainly in the first three years after diagnosis of SLE and was associated with a decreased survival rate (10 year survival 62%). Increased mortality was found in male patients with lupus nephritis over 25 years of age and in female patients with lupus nephritis under 25 years of age, while renal failure rates did not differ between these groups. Treatment of lupus nephritis with high dose prednisone alone or in combination with immunosuppressants did not result in differences in patient survival or renal function preservation. It was concluded that clinical variables are a reliable guide in the management of patients with SLE, and routine use of renal biopsy in these patients is rejected.

Systemic lupus erythematosus. I. Outcome and survival: Dutch experience with 110 patients studied prospectively.

This report presents an analysis of the cumulative survival in 110 well defined patients with systemic lupus erythematosus (SLE) who were followed up over a prolonged period of time. Special attention was paid to possible differences between patients who died and those who were still alive at the end of the study. Of the 110 patients with SLE, 96 (87%) were still alive after 10 years; the cumulative survival for men was 69% (11/16) and for women 90% (85/94). Patients who never developed a new exacerbation after the diagnosis for SLE had been established had a 10 year survival of 100%; for patients with one, two, or three exacerbations the 10 year survival was 91%, 69%, and 33% respectively. From these prospective studies it was found that the exacerbation frequency is most closely related to survival. Disease symptoms of renal involvement or neurological involvement, or both, present at the onset or at the moment the SLE diagnosis was established, were predominantly seen in patients who died during the follow up.

Systemic lupus erythematosus. II. Observations on the occurrence of exacerbations in the disease course: Dutch experience with 110 patients studied prospectively.

The incidence of exacerbations in the disease course was investigated in 110 patients with systemic lupus erythematosus (SLE) who were studied prospectively at our institute for lupus research. At the time of disease onset and diagnosis the male patients were much older than the female patients (about 10 years); exacerbation frequency during follow up was increased in the male patients. The follow up data showed that if a patient with SLE was prone to develop an exacerbation this mostly took place within the first five years of follow up. It could be calculated that after fulfilling the American Rheumatism Association criteria only 56% (62/110) of the patients developed a subsequent exacerbation. Features at the time of diagnosis, distinguishing those patients who developed a subsequent exacerbation from those who did not, were haemolytic anaemia, the presence of anti-Sm antibodies, and a falsely positive serological test for syphilis. At the time of diagnosis, however, the prevalences of these features were low; for haemolytic anaemia, anti-Sm antibodies, and a falsely positive serological test for syphilis they amounted to 40%, 5%, and 12% respectively.

Elevated plasma levels of the anaphylatoxins C3a and C4a are associated with a fatal outcome in sepsis.

PURPOSE AND PATIENTS AND METHODS: Both complement and contact system of coagulation have been implicated in the pathophysiology of sepsis. We therefore measured levels of the complement activation products C1-C1-inhibitor complexes and C3a in serial plasma samples (obtained every six hours) from 48 patients with clinically suspected sepsis, and related these levels to the clinical outcome. C4a was also measured in samples obtained on admission. RESULTS: C3a levels were elevated in 47 patients at least once during the observation period. These levels appeared to be considerably higher in patients who died than in patients who survived. This difference was found for the levels on admission (p = 0.0003), as well as for the highest (p = 0.0010) and the lowest (p less than 0.0001) levels encountered in each patient. The mortality in patients with plasma C3a levels of 13 nmol/liter or less on admission (27 patients) was 33 percent, compared with 86 percent in patients with levels of 14 nmol/liter or more. Patients with septic shock had significantly higher C3a levels than normotensive patients (p values between 0.046 and 0.004). No significant differences in C3a were found between patients who had respiratory distress syndrome and those who did not. C4a levels in plasma samples obtained on admission were elevated in 43 patients. These levels correlated very significantly with C3a levels (p less than 0.0001), and showed similar associations with a fatal outcome. C1-C1-inhibitor complexes were elevated in 23 patients at least once during the observation period. These patients had significantly higher levels of C4a and C3a than patients with normal amounts of C1-C1-inhibitor complexes. Patients who died had higher levels of C1-C1-inhibitor complexes than patients who survived. However, this difference was not significant. CONCLUSION: On the basis of our results, we propose that activation of the complement system via the classical pathway is involved in the development of fatal complications in sepsis.

Antibodies to components of neutrophil cytoplasm: a new diagnostic tool in patients with Wegener's granulomatosis and systemic vasculitis.

Eleven patients with symptoms highly suggestive of Wegener's granulomatosis are described. In spite of extensive investigation, only in two patients was a firm histological diagnosis of Wegener's granulomatosis obtained, while the remaining patients were either diagnosed as having unclassifiable systemic vasculitis or had no histological diagnosis made. This sometimes resulted in diagnostic and therapeutic delay and irreversible organ damage. Antibodies to components of neutrophil cytoplasm--recently demonstrated to be specific for Wegener's granulomatosis--were detected by indirect immunofluorescence in 10 of 11 patients, and it appears likely that antibodies to components of neutrophil cytoplasm will prove to be of great value in early diagnosis.

Increased systemic microvascular albumin flux in septic shock.

Lymph/plasma (L/P) albumin ratios were followed in a patient with a traumatic thoracic duct lymph fistula, during septic shock when lymph flow was high and at recovery when lymph flow was low. Higher albumin ratios were found during the former. On both occasions, the P-L difference of radioactive counts/min per gram was followed for 6 h after i.v. injection of 51Cr human serum albumin (HSA). Equilibration half times between plasma and lymph amounted to 0.85 h during septic shock and 2.49 h at recovery. The data indicate that systemic microvascular albumin flux had increased during shock in our patient. Increased permeability may have been responsible.

Predictive value of complement profiles and anti-dsDNA in systemic lupus erythematosus.

In a prospective study of 143 patients with systemic lupus erythematosus (SLE) the relation between clinical exacerbations, anti-dsDNA levels, and serum levels of complement components, C1q, C4, C3, C5, and C9 was investigated. In 33 out of these 143 patients a major clinical exacerbation of the disease developed. Evaluation of anti-dsDNA levels in relation to disease activity confirmed our earlier finding that anti-dsDNA levels rose before a major exacerbation and decreased after it. In the remaining 110 SLE patients a nearly constant anti-dsDNA level was seen, but none of these patients experienced a major exacerbation. In the 21 SLE patients who developed deterioration in renal function a decrease of C4 followed by decreases of C1q and C3 levels was seen first, starting about 25 to 20 weeks before the first signs of renal involvement. In the 12 SLE patients who developed an exacerbation without renal involvement an inconsistent profile of the complement components C4, C1q, and C3 was observed. C5 levels were hardly affected at all, while C9 levels were in general higher than normal during the exacerbation, irrespective of the type of exacerbation. These results show that, by following the complement and anti-dsDNA profiles, not only can exacerbations be predicted but also a pointer can be obtained about the pattern of disease well before the first clinical signs of an exacerbation appear.