Systemic absorption of FD&C blue dye associated with patient mortality.

The addition of FD&C blue dye to enteral feeds is a common practice in hospitals to detect aspiration. However, the degree of systemic absorption and safety of this dye in critically ill patients has not been studied. A patient with sepsis who died after systemic absorption of FD&C blue dye No1 is described.

Influence of diclofenac (group of nonsteroidal anti-inflammatory drugs) on fracture healing.

INTRODUCTION: Nonsteroidal antirheumatics (NSAR; NSAID) are often used in patients with fractured bones for analgetic reasons. This animal experiment was performed to determine the influence of NSAR on the process of fracture healing. As an alternative, tramadol, the centrally acting analgetic without peripheral effects, was included in this experiment. MATERIALS AND METHODS: Wistar rats were operated on by a transverse osteotomy of the proximal tibia of the left leg. The fracture was stabilized by intramedullary nailing (healing period 21 days). All drugs were applied orally twice a day. The animals were divided into four groups with 10 rats each: Group 1 was treated with placebo (P), group 2 with tramadol (T; 20 mg/kg body weight/day), group 3 with diclofenac sodium (DS; 5 mg/kg bw/day) for 7 days followed by 14 days of placebo, group 4 with diclofenac sodium (DL; 5 mg/kgbw/day) over 21 days. On day 21 the rats were killed, and each leg was examined by X-ray, then the tibia was examined by CT scan, three-point bending, and histology. RESULTS: The results of CT and three-point bending showed that rats treated by diclofenac presented with delayed fracture healing compared with those treated by placebo or tramadol. Bone density in CT was highest in group 1 (mean 611.4+/-50.1 mg/ml), followed by group 2 (mean 542.5+/-29.5 mg/ml). Groups 3 (mean 411+/-34.0 mg/ml; p=0.006) and 4 (mean 395.2+/-15.4 mg/ml; p=0.009) were significantly lower. The stability of the bones, as measured by the breaking force ( F(max)), was highest in group 1 (mean 45.8+/-19.0 N), followed by group 2 (mean 39.0+/-7.9 N; NS); group 3 (mean 20.6+/-7.8 N; p=0.01) was significantly lower than the placebo animals, followed by group 4 (mean 26.5+/-8.3 N; p=0.03). Similar results were shown for bending stiffness: group 1 (mean 1404.6+/-611.4 Nmm/mm), group 2 (mean 1033.2+/-232.1 Nmm/mm; NS), group 3 (mean 564.2+/-457 Nmm/mm; p=0.045), and group 4 (mean 494.8+/-340.2 Nmm/mm; p=0.028). There were no significant differences between groups 1 and 2 and between groups 3 and 4, respectively. Diclofenac serum levels on day 21 in rats with long-term diclofenac application (mean 301.4+/-83.3 ng/ml) were comparable to those in humans. CONCLUSION: Oral application of diclofenac significantly delayed fracture healing in rats. This effect might be comparable to other NSAR and fracture healing in humans.

Mycobacterium szulgai osteomyelitis.

Mycobacterium szulgai is a rare cause of human infections, and when present it is mostly known to cause lung infection. We report the first case of isolated Mycobacterium szulgai osteomyelitis in a 68-year-old woman on chronic immunosuppressive therapy. Review of the literature revealed a total of three other cases of M. szulgai osteomyelitis. In all these cases there was evidence of hematogenous or contiguous spread, including one with extensive dissemination. Pulmonary M. szulgai infections tend to occur in patients with chronic lung disease and/or concomitant lung infections, whereas osteomyelitis tends to occur in patients who have severe immunosuppression secondary to disease or drugs.

Gene therapy for AIDS.

The absence of effective treatments makes AIDS one obvious candidate among the infectious diseases which might be treated by somatic gene therapy. Since HIV1 predominantly infects cells of the haematopoietic system, multipotent stem cells or more mature CD4+ cells constitute potential targets for the introduction of a foreign antiviral gene that will inhibit HIV1 replication and/or spread. Reimplantation of the genetically-modified cells into HIV-infected patients should theoretically allow the repopulation of the host with HIV1-resistant CD4+ cells that might be able to control virus propagation in vivo. Alternatively, increased knowledge of the immunological mechanisms involved in the control of virus infection and propagation has led to the development of different strategies to augment host anti-HIV1 cytotoxic T lymphocyte responses in an effort to prevent virus spread and, hence, the onset of AIDS. While the therapeutic value of such approaches still remains unknown, these experimental treatments hold real promise that require thorough clinical evaluation.

Influence of sample temperature on reflectance photometry and electrochemical glucometer measurements.

OBJECTIVE: A study was conducted to determine the influence of sample temperature on manual reflectance photometers, automatic reflectance photometers, and electrochemical glucometers. RESEARCH DESIGN AND METHODS: Aqueous and blood-based control solutions were tested at temperatures ranging from 25 to 44 degrees C. With the Accu-Chek 3, One Touch, and Satellite G glucometers, multiple glucose determinations were performed on each sample. RESULTS: The results indicate that the manual reflectance photometry glucometer is prominently influenced by variation in sample temperature. The effect of sample temperature is greatest at high glucose levels. CONCLUSIONS: Caution may be required in the interpretation of manual reflectance photometry glucometer measurements in febrile or hypothermic diabetic patients.

[Gene therapy for hereditary and acquired human diseases]. / Thérapie génique de maladies humaines héréditaires et acquises.

Cystic Fibrosis (CF) and AIDS are primary candidate disorders to be treated by gene therapy, owing to their lethality and the absence of efficient clinical treatments. Treatment of CF by gene therapy will require the transfer of the functional CFTR cDNA into the diseased human airway epithelia since mutations within the CFTR gene are responsible for CF. We have therefore cloned the human CFTR cDNA and developed a recombinant E1-deleted adenoviral vector carrying a CFTR expression cassette. We demonstrated in vitro the ability of this vector to efficiently transduce human lung cells isolated from CF patients and to correct their phenotype. Efficient in, vivo delivery of the CFTR cDNA to the airways of cotton rats and rhesus monkeys was also obtained and no dissemination of the recombinant viral vector in other tissues than the airways was observed. We have therefore designed a phase I clinical trial involving CF patients. In contrast to the monogenic CF disease, the mechanisms of AIDS pathogenesis still remain poorly understood. Such limited knowledge of the disease constitutes a serious restriction to the development of a rational gene therapy strategy for AIDS. Since HIV, the causative agent of AIDS, predominantly infects cells of the hematopoietic system, pluri- or multipotent stem cells may constitute potential targets for the introduction of a foreign anti-HIV gene that will inhibit HIV replication and/or spread. Reimplantation of the genetically modified stem cells into asymptomatic HIV-infected patients should theoretically allow the repopulation of the host's immune system with mature CD4+ cells expressing novel molecules that interfere with viral replication, thus slowing the progression of AIDS. We identified several new transdominant inhibitors derived from the viral TAT and REV proteins and showed their ability to confer to human CD4 lymphocytes resistance against HIV1 infection. Retroviral vectors carrying these potential therapeutic genes have been developed and are currently being tested in vivo in newly developed transgenic animal models, in humanized SCID mice and in macaques.

Foscarnet-induced severe hypomagnesemia and other electrolyte disorders.

OBJECTIVE: To report a case of possible foscarnet-induced severe hypomagnesemia and other electrolyte disorders. CASE SUMMARY: An AIDS patient experienced an exacerbation of cytomegalovirus retinitis and was treated with foscarnet. The patient experienced muscle twitches, tremulousness, and anxiety on day 17 of foscarnet therapy. Laboratory results indicated hypomagnesemia, hypocalcemia, hypokalemia, and hypophosphatemia. After electrolyte supplementation and discontinuation of foscarnet, the symptoms resolved and laboratory indices returned to normal. DISCUSSION: Electrolyte disorders associated with foscarnet are reviewed. Severe hypomagnesemia occurred in this patient and published literature is highlighted. In addition, known and/or possible mechanisms of the disorders are discussed. CONCLUSIONS: It is probable that foscarnet contributed to the electrolyte disorders and symptomatology in this patient. Electrolytes must be monitored frequently during foscarnet therapy. Also, concomitant therapy with antianxiety medications that may mask the symptoms of electrolyte disorders should be undertaken with caution.

Utilization and metabolism of NAD by Haemophilus parainfluenzae.

The utilization of exogenous nicotinamide adenine dinucleotide (NAD) by Haemophilus parainfluenzae was studied in suspensions of whole cells using radiolabelled NAD, nicotinamide mononucleotide (NMN), and nicotinamide ribonucleoside (NR). The utilization of these compounds by H. parainfluenzae has the following characteristics. (1) NAD is not taken up intact, but rather is degraded to NMN or NR prior to internalization. (2) Uptake is carrier-mediated and energy-dependent with saturation kinetics. (3) There is specificity for the beta-configuration of the glycopyridine linkage. (4) An intact carboxamide groups is required on the pyridine ring. The intracellular metabolism of NAD was studied in crude cell extracts and in whole cells using carbonyl-14C-labelled NR, NMN, NAD, nicotinamide, and nicotinic acid as substrates in separate experiments. A synthetic pathway from NR through NMN to NAD that requires Mg2+ and ATP was demonstrated. Nicotinamide was found as an end-product of NAD degradation. Nicotinic acid mononucleotide and nicotinic acid adenine dinucleotide were not found as intermediates. The NAD synthetic pathway in H. parainfluenzae differs from the Preiss-Handler pathway and the pyridine nucleotide cycles described in other bacteria.

Paroxysmal nocturnal hemoglobinuria associated with the acquired immunodeficiency syndrome.

Pancytopenia is a well-recognized manifestation of clinical illness related to human immunodeficiency virus infection. The mechanism of this has been debated, but has been thought to relate either to a nonspecific marrow suppressive effect of opportunistic infections, or to direct involvement of bone marrow hematopoietic precursors as a target of human Immunodeficiency virus. We report the unique temporal association of the acquired immunodeficiency syndrome and paroxysmal nocturnal hemogloblnuria.

Comparative in vitro activities of ampicillin, BMY 28142, and imipenem against Mycobacterium avium complex.

The in vitro activity of ampicillin, BMY 28142, and imipenem was evaluated against 21 clinical isolates of Mycobacterium avium complex by both a broth and an agar dilution method. The MIC90 by broth dilution for ampicillin, BMY 28142, and imipenem was 16 micrograms/ml, 8 micrograms/ml, and greater than 32 micrograms/ml, respectively. The MIC90 by agar dilution for ampicillin and BMY 28142 was 16 micrograms/ml.

Comparison of four beta-lactamase inhibitors in combination with ampicillin against Mycobacterium tuberculosis.

The in-vitro activity of a beta-lactamase inhibitor (clavulanic acid, sulbactam, BL-P2013 or BL-P2090) in combination with ampicillin against 13 isolates of Mycobacterium tuberculosis was determined by broth dilution. The agents were tested in 1:1 molar ratio of ampicillin to beta-lactamase inhibitor. The beta-lactamase inhibitors alone did not inhibit growth at the highest concentration tested. The MIC90 for ampicillin alone was greater than 32 mg/l. Clavulanic acid plus ampicillin was the most active combination with an MIC90 of 11 microM (4 mg/l of ampicillin). The MIC90 of ampicillin in combination with sulbactam, BL-P2013 or BL-P2090 was 23 microM (8 mg/l of ampicillin). A 1:1 ratio of ampicillin to inhibitor was more active than was a 2:1 ratio. The addition of a beta-lactamase inhibitor to ampicillin greatly improves its in-vitro activity against M. tuberculosis.

Negative-pressure isolator for work with hazardous infectious agents in monkeys.

The development, fabrication, and use of a negative-pressure isolator for work with hazardous infectious agents in monkeys or other larger animals are described.