Diagnostic value of signs, symptoms and laboratory values in lower respiratory tract infection.

BACKGROUND: Lower respiratory tract infections (LRTI) account for the majority of all antibiotics prescribed in the clinical practice, irrespective of the fact that most cases are self-limiting. Using the outcome and microbiology findings as gold standard, we determined sensitivity, specificity, positive and negative predictive values of common used signs and symptoms of bacterial LRTI requiring antibiotic therapy. PATIENTS: 243 consecutive patients with suspected LRTI admitted to a tertiary care hospital. RESULTS: Bacterial LRTI requiring antibiotic therapy and self-limiting LRTI were diagnosed in 32 and 86 patients, respectively. Assessing these two groups, sputum, dyspnea, crackles, fever and leukocytes (WBC) were insensitive and unspecific parameters for the diagnosis of bacterial LRTI requiring antibiotic therapy. Cough was sensitive (93.8%) but unspecific (5.8%). The sensitivity of infiltrates, C-reactive protein (CRP) >50 mg/L and procalcitonin (PCT) >0.1 ng/mL was 96.9%, 93.8% and 93.8%, respectively. PCT >0.25 ng/mL showed the highest specificity (97.7%), followed by WBC >16 x 109/L (94.2%) and CRP >100 mg/L (91.9%). The sensitivity of WBC >16 x 109/L was low (37.5%). CONCLUSION: The overall sensitivity and specificity of signs and symptoms for bacterial LRTI requiring antibiotic therapy was poor. Obtaining a chest-X-ray with infiltrates and determining CRP at a cut-off value of 50 mg/L or PCT at a cutoff value of 0.1 ng/mL was required to ascertain the need for antibiotics in LRTI.

Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial.

RATIONALE: In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications. OBJECTIVE: To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia. METHODS: In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 microg/L; discouraged, less than 0.25 microg/L; encouraged, greater than 0.25 microg/L; strongly encouraged, greater than 0.5 microg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome. RESULTS: At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48-0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%. CONCLUSIONS: Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications.

Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and insulin resistance; long-term consequences include diabetes mellitus type 2. The aim of this randomized, double-blind, controlled trial was to investigate whether the thiazolidinedione derivative pioglitazone diminishes insulin resistance and hyperandrogenism and enhances ovulation rates in women with PCOS. Forty premenopausal women with PCOS were randomly allocated to treatment with either pioglitazone (30 mg/d) or placebo for periods of 3 months. Administration of pioglitazone resulted in a remarkable decline in both fasting serum insulin levels (P < 0.02) and the area under the insulin response curve after an oral glucose load (P < 0.02). This represented an increase in insulin sensitivity and a decrease in insulin secretion (P < 0.05). Furthermore, pioglitazone increased serum SHBG (P < 0.05), resulting in a significant decrease in the free androgen index (P < 0.05 compared with placebo). Treatment with pioglitazone was also associated with higher ovulation rates (P < 0.02). Thus, pioglitazone significantly improved insulin sensitivity, hyperandrogenism, and ovulation rates in women with PCOS, thereby providing both metabolic and reproductive benefits.

Increased renovascular response to angiotensin II in persons genetically predisposed to arterial hypertension disappears after chronic angiotensin-converting enzyme inhibition.

OBJECTIVE AND METHODS: Functional changes in the kidneys of healthy men with (FH+) (n = 15) and without (FH-) (n = 15) family history of primary arterial hypertension were examined during administration of low-dose exogenous angiotensin II (A2) (1 ng/kg per min) before and after acute (1 mg intravenous enalaprilat) and chronic (7 days oral enalapril, 30 mg/day) angiotensin-converting enzyme (ACE) inhibition. RESULTS: Before chronic ACE inhibition, A2 increased mean arterial blood pressure (FH+, 8.7 +/- 0.8 mmHg; FH-, 8.9 +/- 0.9 mmHg), plasma immunoreactive A2 (FH+, 21 +/- 2 pg/ml; FH-, 18 +/- 3 pg/ml) and plasma aldosterone (FH+, 64 +/- 7 pg/ml; FH-, 56 +/- 6 pg/ml) to a similar degree in both groups. Chronic ACE inhibition had no impact on A2 blood pressure, plasma A2, or plasma aldosterone effects. A2 significantly increased renal vascular resistance in both groups (FH+, 3956 +/- 462 dyne s cm(-5); FH-, 2219 +/- 550 dyne s cm(-5)), but the effect was more pronounced in FH+ (P = 0.02). Glomerular hemodynamics, estimated by a modified Gomez model, revealed increased afferent and efferent responsiveness to A2 in FH+ subjects. These differences disappeared after chronic ACE inhibition when total, afferent and efferent sensitivities to A2 were similar in both groups. CONCLUSIONS: Systemic blood pressure and plasma aldosterone responses to A2 were similar in men with or without a genetic disposition to primary arterial hypertension. However, our data demonstrate that men with a family history of hypertension have increased renovascular sensitivity to A2, and that chronic ACE inhibition normalizes their sensitivity.

Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial.

BACKGROUND: Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay. METHODS: 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat. FINDINGS: Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%). INTERPRETATION: Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.

Increased high-frequency heart rate variability during insulin-induced hypoglycaemia in healthy humans.

Despite causing sympathetic activation, prolonged hypoglycaemia produces little change in HR (heart rate) in healthy young adults. One explanation could be concurrent parasympathetic activation, resulting in unchanged net effects of autonomic influences. In the present study, hypoglycaemic (2.7 mmol/l) and normoglycaemic (4.7 mmol/l) hyperinsulinaemic clamp studies were performed after normoglycaemic baseline clamp periods with 15 healthy volunteers (seven male; mean age, 27 years) on two occasions in a randomized single-blind cross-over design. Non-invasive indices of cardiac autonomic activity and hormones were measured at baseline and 1 h after the beginning of hypoglycaemia or control normoglycaemia. Plasma insulin levels and mean HR were similar during both conditions. During hypoglycaemia, there was a 485% increase in plasma adrenaline (epinephrine). A shortening of the pre-ejection period by 45% suggested strong sympathetic cardiac activation. High-frequency (0.15-0.45 Hz) HRV (HR variability) increased, indicating a concomitant increase in parasympathetic tone. Thus, during hypoglycaemia-induced sympathetic cardiac activation in healthy adults, parasympathetic mechanisms are involved in stabilizing mean HR.

Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI): report on 23 patients and review of the literature.

The brittle cornea syndrome (BCS) is a generalized connective tissue disorder characterized by corneal rupture following only minor trauma, keratoconus or keratoglobus, blue sclerae, hyperelasticity of the skin without excessive fragility, and hypermobility of the joints. It is inherited as an autosomal recessive trait but the underlying genetic defect remains undetermined. We present 23 patients (11 male) from 13 nuclear families followed at the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, aged 3-28 years at last follow-up. A total of 28 events of corneal rupture were noted in 17 patients (eight male), among whom nine had had bilateral ruptures, and eight had had unilateral ruptures (four of the right cornea), while two had experienced re-rupture 2 and 4 years, respectively, after surgery; six patients (aged 3-21 years) had had no ruptures. We describe the natural history of our cases and discuss them together with those others reported in the literature. Because of similarities between the BCS and the kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VI), both disorders tend to have been confounded. Here, we show that all of our BCS patients tested in this regard had biochemical findings reflective of normal activity of lysyl hydroxylase, characteristically deficient in EDS VI, such as normal urinary total pyridinoline ratios and/or normal electrophoretic migration of collagen chains produced by dermal fibroblasts. The BCS is, therefore, an entity distinct from the kyphoscoliotic type of EDS, which has a much poorer prognosis.

Intraoperative parathormone measurement in patients with primary hyperparathyroidism: a prospective clinical study.

BACKGROUND: The objective of this pilot study was to evaluate the use of intraoperative iPTH measurement in combination with bilateral neck exploration in patients with primary hyperparathyroidism. METHODS: A prospective study was conducted in a single centre university hospital in Switzerland comprising 33 patients with primary hyperparathyroidism undergoing neck surgery. No routine preoperative localisation studies were conducted. Intraoperative iPTH measurement was performed at defined times. Exploration was discontinued when iPTH fell below 15% of baseline. RESULTS: For all patients with adenoma the median serum iPTH decreased to 11.9% (standard deviation 5.5%) of baseline concentrations. All patients with hyperplasia achieved normocalcaemia. At median follow-up of 17.7 weeks neither recurrent nor persistent hypercalcaemia was observed. Eleven patients were explored unilaterally. CONCLUSION: Measurement of intraoperative serum iPTH is a helpful tool in the differentiation of single adenoma from hyperplastic glands. When we call for a strict 78% decrease in serum iPTH from base levels after 10 minutes, measurement of this marker protein even allows differentiation of single- from multi-glandular disease.

Elevated C-reactive protein and homocysteine values: cardiovascular risk factors in hypothyroidism? A cross-sectional and a double-blind, placebo-controlled trial.

Hypothyroidism is associated with premature atherosclerosis and cardiovascular disease. Recently, total homocysteine (tHcy) and C-reactive protein (CRP) emerged as additional cardiovascular risk factors. We first investigated CRP and tHcy in different severities of primary hypothyroidism and in a second study we evaluated the effect of L-thyroxine treatment in patients with subclinical hypothyroidism (SCH) in a double-blind, placebo-controlled trial. One hundred and twenty-four hypothyroid patients (63 with subclinical, 61 with overt hypothyroidism, OH) and 40 euthyroid controls were evaluated. CRP was measured using a latex-based high sensitivity immunoassay; tHcy was determined by a fluorescence polarization immunoassay. tHcy values were significantly elevated in OH (P=0.01). In SCH tHcy levels were not augmented as compared to controls. CRP values were significantly increased in OH (P=0.016) and SCH (P=0.022) as compared to controls. In a univariate analysis tHcy correlated significantly with fT4, vitamin B12, folic acid and creatinine levels. In multiple regression analysis only fT4 (beta=0.33) had a significant effect on tHcy. CRP did not correlate with thyroid hormones. In SCH, L-T4 replacement had no significant effect on either tHcy or CRP levels. This is the first paper to show that CRP values increase with progressive thyroid failure and may count as an additional risk factor for the development of coronary heart disease in hypothyroid patients. In contrast to overt disease, only CRP, but not tHcy values, are affected in SCH, yet without significant improvement after L-thyroxine therapy.

Windows to the ward: graphically oriented report forms. Presentation of complex, interrelated laboratory data for electrophoresis/immunofixation, cerebrospinal fluid, and urinary protein profiles.

BACKGROUND: Automated laboratory analyzers that mass produce data have been linked to information systems for more than two decades, but little progress has been made in developing more comprehensible report forms. Results are still reported in computer-generated printouts containing hundreds of numbers crowded into columns on each printed page. METHODS: We developed three software applications focusing on the graphic presentation of laboratory results. RESULTS: The first application summarizes data for a patient with a monoclonal gammopathy. The report provides a cumulative graphic presentation of immunofixation/electrophoresis data without any additional interpretation, focuses on a color-coded electrophoresis scan, and records up to 5 years on a single page. The second application deals with cerebrospinal fluid analysis. The report calculates relevant data and graphs the complex relationship between albumin and immunoglobulin results from paired serum and cerebrospinal fluid samples. Manually added interpretive text assures an output comprehensible to clinicians in all specialties. The third application produces a report summarizing quantitatively measured urinary marker protein profiles. The report form is generated by a flexible, completely user-definable knowledge-based system. It calculates numerous ratios and formulae, supports reflex testing, supplies an automated interpretation, and generates a specific graphic signature pattern of the results (MDI LabLink proteinuria differentiation). CONCLUSIONS: Increased clinical demand for graphically oriented report forms 5 years after their introduction has provided evidence that these reports transfer complex laboratory data and results to the clinician more effectively. The highest (more than threefold) increase in demand has been for reports for urinary marker protein profiles that feature a largely self-explanatory graphic signature pattern.

Progesterone serum levels during the follicular phase of the menstrual cycle originate from the crosstalk between the ovaries and the adrenal cortex.

BACKGROUND: The preovulatory rise of progesterone is important for ovulation, but both its regulation and its origin are controversial. Three experiments were performed to determine whether follicular phase progesterone arises from the ovary, the adrenal cortex or both. METHODS: The first study was performed in patients scheduled for assisted reproduction, who received a long-acting GnRH agonist either during intake of an oral contraceptive or during the luteal phase of an otherwise untreated menstrual cycle. The second study was also performed during down-regulation with a GnRH agonist: some patients with elevated progesterone levels received dexamethasone (DXM). Others with similarly elevated basal progesterone levels and those with low progesterone levels were not treated with DXM and served as controls. Finally, adrenocorticotrophic hormone (ACTH) tests were performed in normocyclic volunteers both during early and late follicular phase and during intake of a contraceptive pill. RESULTS: During the suppression of endogenous gonadotrophin secretion progesterone levels rose after the administration of ACTH, but not of GnRH. DXM did not prevent the preovulatory rise of the serum progesterone concentration. The ACTH-stimulated concentration of progesterone and of 17alpha-hydroxyprogesterone were significantly reduced during intake of ethinyl estradiol. CONCLUSIONS: Progesterone arises in the adrenal cortex during most of the follicular phase, whereby its function is modulated by an unknown ovarian factor, which is suppressed by ethinyl estradiol. The source of progesterone shifts towards the ovaries prior to ovulation.