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Editor's note: Joe Ognibene created audio clips to enable the reader to hear Hermann Baumann and his horns on each of the recordings underlined. These can be accessed by scanning [...]

As a teenage horn student I was fortunate to be in the right place at the right time: Claremont, California in the summer of 1975, two years after the fifth [...]

There are several reasons to micronise APIs in a solid-dosage 1 formulation. Many new drug molecules are poorly soluble, and one means to enhance solubility is to enlarge surface area [...]

Micronized APIs help to improve solubility and are appropriate in low-dose formulations. Wet or dry granulation is typically used instead of direct compression (DC) in solid-dosage formulations to achieve homogenity [...]

Parteck ODT is a newly introduced ready-to-use excipient for fast melt tablets. In this study, we tested its disintegration behaviour and drug release characteristics using two different actives and showed [...]

The patient population at risk for opportunistic pulmonary infections has increased during the last decade. The spectrum of organisms causing opportunistic infections has also grown. With an ever broader list of potential therapeutic options and a growing differential diagnosis, a specific diagnosis of the cause of pulmonary disease becomes more important. Recent microbiologic advances have helped to facilitate the laboratory diagnosis of some of these agents. Immunoassays are available for the detection of antigen in nasopharyngeal secretions respiratory syncytial virus, influenza), in serum (Cryptococcus species), and in urine (Legionella or Histoplasma species). Rapid-culture techniques are available for the culture and detection of various viruses, including cytomegalovirus. Molecular probes can now assist in the rapid identification of Mycobacterium tuberculosis and some fungi. In the near future, polymerase chain reaction-based techniques may assist in the detection of Pneumocystis carinii and Legionella, Chlamydia, Mycoplasma, and Mycobacteria species. An expeditious evaluation of pulmonary disease requires an understanding of the differential diagnosis of likely causes of pulmonary disease in specific immunosuppressed patient populations, an understanding of the most appropriate specimens to process for these diagnoses, and an understanding of the limitations (sensitivity and specificity) of these diagnostic tests. An understanding of the most appropriate specimens and tests in a given institution should allow for early, relatively specific treatment of many potentially life-threatening infections., The availability of polymerase chain reaction tests may be helpful in identifying the specific cause of disease but may be costly and as yet impractical for routine use. Polymerase chain reaction tests are tests that rapidly multiply the infectious organism for quicker and more accurate identification. Researchers outlined the current procedures and described the preliminary use of polymerase chain reaction tests for identifying organisms that cause infections in the lung and respiratory tract. Doctors currently use antibody tests on fluid samples from the lung or bronchial tubes to identify Legionella infections. An antibody test called shell vial culture can simply and quickly identify viral infections. Blood tests can identify mycoplasma and chlamydia pneumonia, while staining tests can quickly identify Pneumocystis carinii infections. A fluorescent staining test has proven effective in identifying fungal infections. Individual clinics may wish to invest in using polymerase chain reaction tests that identify organisms prevalent in their clinics.

Background: Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number of solid tumors, including ovarian cancer and breast cancer. Purpose: Our purpose was to conduct a phase 11 clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF). Methods: A prospective phase 11 clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/[m.sup.2] paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 [mu]g/kg per day was given to ameliorate myelosuppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 [mu]g/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy. Results: Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients; 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy. Conclusions: We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower dose in similar cohorts of patients treated without G-CSF. Comparison of phase 11 studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer. [J Natl Cancer Inst 86:18-24, 1994]

Study objective: To investigate the pathogenesis of lung injury in Pneumocystis carinii pneumonia and nonspecific interstitial pneumonitis (NIP), common pulmonary complications of human immunodeficiency virus (HIV) infection. The efficacy of [...]

Study objective: To review the clinical and laboratory findings in a large number of patients with pneumococcal bacteremia in the 1980s and identify risk factors associated with increased mortality. Design: [...]

* Objective: To determine the incidence and characterize the occurrence of cardiac toxicity with high-dose ifosfamide. * Design: Retrospective chart review. * Setting: Biomedical research referral center. * Patients: Fifty-two consecutive patients with advanced lymphoma or carcinoma enrolled in phase I trials of high-dose ifosfamide as part of combination chemotherapy with autologous bone marrow transplantation. * Interventions: Patients were given escalating doses (10 to 18 g/[m.sup.2]) of ifosfamide in combination with carboplatin and etoposide or with lomustine and vinblastine. * Measurements: The chart review focused on clinical, radiographic, or electrocardiographic evidence of cardiovascular dysfunction. Data from invasive hemodynamic monitoring, radionuclide cineangiography, and echocardiography were also reviewed. * Results: Nine of the patients treated with ifosfamide developed congestive heart failure (17%; 95% Cl, 8% to 30%). Eight of these patients, experiencing dyspnea, tachycardia, weight gain, and signs of pulmonary edema, required admission to an intensive care unit. Left ventricular contractility was found to be depressed when evaluated by radionuclide cineangiography, echocardiography, or both. Most patients responded to diuretic, vasodilator, and inotropic therapies. Two patients developed malignant ventricular arrhythmias. One patient died of intractable cardiogenic shock. Five patients died of multiorgan failure, despite showing improvement in left ventricular ejection fraction. Three patients survived and regained baseline left ventricular ejection fraction. * Conclusions: High-dose ifosfamide is associated with severe but usually reversible myocardial depression and malignant arrhythmias., Treatment with high doses of ifosfamide may cause congestive heart failure in some patients. Ifosfamide is a drug used to treat patients suffering from cancer or advanced lymphoma who undergo bone marrow transplantation. Among 52 patients with cancer or advanced lymphoma who were treated with increasing doses of ifosfamide in combination with other anti-cancer drugs, nine (17%) developed congestive heart failure. Patients developed congestive heart failure an average of 12 days after starting treatment with ifosfamide. Eight patients were admitted to the intensive care unit to undergo treatment for severe congestive heart failure. Symptoms developed by the patients before admission to the hospital included shortness of breath, rapid heart beat, weight gain and collection of fluid in the lungs. One patient died from complications associated with the development of congestive heart failure.

We assessed qualitative and quantitative differences in surfactant lipid composition of bronchoalveolar lavage (BAL) fluid in patients with acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii (PC) pneumonia. Five normal volunteers and 27 patients with human immunodeficiency virus (HIV) infection underwent BAL for evaluation of possible pulmonary infection. Bronchoalveolar lavage studies in eight patients were negative for PC organisms, and 19 were positive. Pneumocystis carinii pneumonia was graded (mild vs moderate to severe) by initial alveolar-arterial oxygen gradient. Bronchoalveolar lavage fluid was centrifuged, the lipids were extracted from the supernatant, and total lipid profiles of dephosphorylated glycerolipids were analyzed as trimethylsilylether derivatives by high temperature gas-liquid chromatography. Phospholipase [A.sub.2] levels were determined using a radiolabeled E coli membrane method. Compared to the normal volunteers (109 ± 13 Μg/5 ml) and the PC negative group (107 ± 13 Μg/5 ml), total BAL lipid was reduced for both the mild PC pneumonia group (73 ± 10 Μg/5 ml) and the moderate to severe PC pneumonia group (46 ± 4 Μg/5 ml). There was a parallel reduction of diacylglycerol lipids: normal volunteers, 52 ± 7 Μg/5 ml; PC negative, 52 ± 9 Μg/5 ml; mild PC pneumonia, 35 ± 7 Μg/5 ml; and moderate to severe PC pneumonia, 15 ± 2 Μg/5 ml. Phospholipase [A.sub.2] activity in moderate to severe PC pneumonia was twice that of the PC negative patients, and 30 times that for normals. The data demonstrate a marked diminution in surfactant glycerophospholipid in patients with AIDS and PC pneumonia and suggest a potential role for surfactant abnormality in the pathophysiology of this disease. (Chest 1992; 102:1730-36), Pneumocystis carinii (PC) pneumonia is the leading cause of serious lung disease in patients infected with the human immunodeficiency virus (HIV).[1] Although advances have been made in early diagnosis,[2] prophylaxis[3] [...]

Patients with HIV (human immunodeficiency virus) infections have a high risk of developing other life-threatening infections. Patients with severe HIV infections should be treated with drugs to prevent an infection with Pneumocystis carinii (P. carinii), a fungus that causes pneumonia. Pentamidine and trimethoprim/sulfamethoxazole have been shown to be effective in treating pneumonia caused by P. carinii. However, it has been reported that treatment with pentamidine in the form of an aerosol reduces the sensitivity of medical procedures used to diagnose pneumonia. The method of choice for diagnosing P. carinii pneumonia in patients with HIV is to examine a sample of sputum (mucus coughed up from the lungs). This article describes the results of a study designed to evaluate the effect of treatment with aerosol pentamidine on the diagnosis of pneumonia in patients with HIV. A total of 348 sputum samples from patients with HIV were examined, 193 from patients treated prophylactically with pentamidine, 29 from patients treated with other drugs and 126 from patients not receiving drug therapy. Fifty-four of the 72 cases of pneumonia found were diagnosed using the sputum samples. Forty-four of the cases of pneumonia occurred in patients not receiving drug therapy and 28 of the cases occurred in patients treated with pentamidine. Treatment with pentamidine reduced the diagnostic sensitivity of the induced sputum test by 28 percent (from 92 percent to 64 percent). Despite the reduction in sensitivity, it is concluded the induced sputum test should remain the first test used to diagnose P. carinii pneumonia in patients with HIV. (Consumer Summary produced by Reliance Medical Information, Inc.)

Antibiotics are de rigueur, of course, but the standard of care includes ICU monitoring and cardiac support based on fluid resuscitation. Steroids are out; monoclonal antibodies are coming in. EXPRESS [...]

Septic shock is the most common cause of death among patients in the intensive care units. This condition is associated with sepsis, widespread infection (usually by gram-negative organisms), the release of endotoxins, and deterioration of cardiac and respiratory functions. The number of cases of septic shock has increased dramatically over the past several decades and is believed to still be increasing. Many factors contributing to this increase have been identified: increased use of immunosuppressive and chemotherapeutic agents, increased use of intravascular catheters and other invasive devices for diagnostic and therapeutic use, and increased number of infections resistant to antibiotics. The pathogenesis of this condition is very complex and it often cannot be distinguished from the underlying diseases present in critically ill patients. Prompt treatment of septic shock is essential and should involve management and close monitoring in an intensive care unit (ICU). Treatment in the ICU, managed by a critical care physician, involves the use of sophisticated techniques and equipment to monitor heart rate, blood pressure, and all related cardiac and respiratory parameters. Broad spectrum antibiotics are administered to treat all possible bacterial causes of the sepsis and therapy should be adjusted after the specific organisms are identified. Immediate treatment of the low blood pressure (hypotension) is essential and is accomplished by the administration of intravenous fluids. These recommendations have resulted in increased patient survival. Although physicians generally understand the treatment of septic shock, additional knowledge is needed to understand the steps in its development and ways to interrupt the key steps in the process. (Consumer Summary produced by Reliance Medical Information, Inc.)

Septic shock in humans is usually characterized by a high cardiac output, a low systemic vascular resistance, reversible depression of left ventricular ejection fraction, and transient left ventricular dilatation. The [...]

Alternatives to Conscious Sedation Conscious sedation enhances the safety, technical ease, and comfort of many pediatric procedures.[1-3] Monitored conscious sedation is now standard practice for children in many different settings [...]

Abstract We evaluated the intrasession and intersession reliability of acoustic rhinometry in measuring nasal cross-sectional areas in 10 subjects. Subjects were measured under three conditions: with a Breathe Right nasal [...]

EDOARDO MANNUCCI, MD [1] AGOSTINO OGNIBENE, MD [2] FRANCESCO CREMASCO, MD [1] GIANLUCA BARDINI, MD [1] ANTONELLA MENCUCCI, MD [1] ENRICA PIERAZZUOLI, MD [1] SILVIA CIANI, BS [1] GIANNI MESSERI, [...]

Matsuda and De Fronzo [1] have recently described a new insulin sensitivity index (ISI) calculated from blood glucose and insulin after an oral glucose load, which is highly correlated to [...]

GLP-1 is a gastrointestinal hormone which stimulates insulin secretion and promotes satiety. GLP-1 and drugs that inhibit its degradation, such as dipeptidyl-peptidase IV inhibitors, have been proposed as therapeutic tools [...]

It has been hypothesized that the impairment of secretion of the insulinotropic gut hormone GLP-1 could contribute to the pathogenesis of type 2 diabetes. The aim of this study was [...]

Study objective: To assess the risk for complications with the use of sedation and analgesia techniques in pediatric fiberoptic bronchoscopy. Design: A retrospective case series. Setting: The ICU of a [...]

Aim of this study is the assessment of the effects of metformin on the secretion of GLP-1 induced by oral glucose in obese patients. In order to assess GLP-1 secretion [...]

Opportunistic infections, which occur because of a patient's altered physiological state, are the major cause of life-threatening disease and death in patients infected with the human immunodeficiency virus (HIV). HIV infection depletes CD4 or helper T cells, a type of immune cell involved in increasing the production of antibodies, immune proteins that bind to and inactivate foreign particles. The depletion of CD4 cells results in a weakened immune system and increased risk of developing opportunistic infections. The number of CD4 cells has been shown to be a good indicator of the immune activity in HIV-infected patients, and have been used to predict whether an HIV-infected patients will develop AIDS (acquired immunodeficiency syndrome). The usefulness of CD4 counts in diagnosing pneumonia in 100 HIV-infected patients was assessed. CD4 counts were less than 200 cells per cubic millimeter before 46 of 49 cases of pneumocystis pneumonia, before all eight cases of cytomegalovirus pneumonia, all seven cases of Mycobacterium avium-intracellular infection, and 19 of 21 cases of infection with Cryptococcus neoformans. Thus, pneumocystis pneumonia, cytomegalovirus pneumonia, and lung infection by C. neoformans and M. avium-intracellular are not likely to occur in patients with CD4 counts greater than 200 to 250 cells per cubic millimeter, or a CD4 percent of circulating lymphocytes of 20 to 25 percent. Patients with CD4 counts less than 200 cells per cubic millimeter may benefit from prophylaxis against pneumocystis infection. (Consumer Summary produced by Reliance Medical Information, Inc.)

A study was conducted to assess the use of the sputum induction technique as a means for diagnosing pneumocystis carinii (P.carinii) pneumonia in children infected with the human immunodeficiency virus (HIV, the virus that causes acquired immunodeficiency syndrome, AIDS). The data demonstrate that sputum induction can provide a pulmonary (lung) specimen adequate to diagnose P. carinii pneumonia. Sputum induction procedure includes withholding food for 4 hours, having patients inhale a mist generated by an ultrasonic nebulizer and coughing up sputum into special cups. The sputum-based test eliminated the need to perform invasive bronchoscopy or open lung biopsy, methods commonly used to obtain samples for laboratory analysis for the presence of P. carinii in HIV-infected patients. The number of immunosuppressed children prone to P. carinii infection is increasing, therefore, sputum induction should become an early step in establishing the diagnosis of this disease.