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Biomedical subjects

J M Shapiro

Publications and source records attributed to J M Shapiro.

At least 19 recordsLinked to original sources
PubMed2006

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.

Bayes Theorem↗
PubMed1998

Unilateral absent pulmonary perfusion due to bronchogenic carcinoma.

Ventilation-perfusion lung scans are commonly done in the diagnosis of pulmonary thromboembolic disease. We describe a patient in whom absent perfusion involving an entire lung was due to bronchogenic carcinoma. Echocardiography and chest computed tomography were essential tests in evaluating a nonembolic etiology.

Bronchoscopy↗
PubMed1996

Early bronchoscopic diagnosis of concomitant tuberculosis and Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection.

Pulmonary infections, including mixed infections, are common in patients with human immunodeficiency virus (HIV), and a specific diagnosis is desirable to direct therapy. In a retrospective study of patients suspected of having Pneumocystis carinii pneumonia, we examined the usefulness of fiberoptic bronchoscopy in the immediate diagnosis of tuberculosis. In 267 patients, pneumocystis pneumonia was diagnosed in 115 (43%), of whom 5 (4%) also had concomitant tuberculosis. Bronchoalveolar lavage gave an immediate diagnosis of tuberculosis by positive acid-fast bacilli stain in 3 patients, while the transbronchial biopsy was suggestive in a fourth. Four of these patients developed respiratory failure, and 2 died. In patients with pneumocystis pneumonia, respiratory failure was significantly more common in those with tuberculosis (P = .0077). In 156 (58%) of the 267 cases, bronchoalveolar lavage was negative for pneumocystis pneumonia, while tuberculosis was diagnosed in 14 (9%), and an immediate diagnosis was made in 10 (71%). In a series of HIV-infected patients suspected mainly of having pneumocystis pneumonia, tuberculosis was found instead in 19 (7%), and both diseases were present in 5 (2%). Bronchoscopy provided an early diagnosis of tuberculosis in 63%. Patients with concomitant pneumocystis pneumonia and tuberculosis had a high rate of respiratory failure.

AIDS-Related Opportunistic Infections↗
PubMed1995

Pressure measurements in the normal and occluded rabbit maxillary sinus.

Occlusion of the maxillary ostium is considered to be a key factor in the pathogenesis of maxillary sinusitis. In this study, the authors determined the effect of ostial occlusion on pressure in the rabbit maxillary sinus which, like most humans, has only one ostium. We compared pressures in the normal and occluded maxillary sinus and the nasal cavity during spontaneous breathing in anesthetized adult animals. Serial pressure measurements were obtained from sinuses with patent ostia in nasal-breathing rabbits and with occluded ostia in both nasal-breathing and tracheotomized animals. Sinuses with patent ostia showed pressure curves synchronous with the respiratory cycle. Inspiratory and expiratory pressures in the nasal cavity and the sinus were isobaric. Sinuses with occluded ostia initially developed a positive pressure followed by a negative pressure that reached a subatmospheric plateau of -28.2 +/- 7.3 mm H2O (mean +/- standard deviation [SD]) within 20 to 50 minutes. This is the first quantitative study of sinus pressures using the rabbit as an animal model. The findings may contribute to a better understanding of the role of ostial occlusion in the pathogenesis of maxillary sinusitis in humans.

Animals↗
PubMed1994

Respiratory failure in pregnancy due to Pneumocystis carinii: report of a successful outcome.

BACKGROUND: The incidence of infection with the human immunodeficiency virus (HIV) is rising rapidly among women of reproductive age. Pneumocystis carinii pneumonia during pregnancy may be the first manifestation of HIV infection. If respiratory failure ensures, the outcome has been reported as almost invariably fatal. CASE: A 31-year-old African-American woman at 28 weeks' gestation was admitted with bilateral perihilar interstitial infiltrates. Laboratory evaluation revealed hypoxemia and an elevated serum lactic dehydrogenase level. Although she denied risk factors for HIV infection, she was treated immediately for P carinii infection with trimethoprim-sulfamethoxazole and methylprednisolone. Her respiratory status deteriorated and she required intubation. Bronchoscopy confirmed the diagnosis, and CD4 lymphocyte depletion confirmed immunosuppression. The patient responded to treatment and recovered completely. CONCLUSION: A high index of suspicion must be maintained for the diagnosis of P carinii and previously unsuspected HIV infection during pregnancy. The early manifestations may be subtle and progress over weeks until respiratory failure rapidly ensues. With timely diagnosis and management, the outcome of P carinii pneumonia in pregnancy can be successful.

AIDS-Related Opportunistic Infections↗
PubMed1993

Changes in hepatocyte NADH fluorescence during prolonged hypoxia.

Deprivation of oxygen reduces oxidative phosphorylation and rapidly causes an increase in cellular NADH which can be monitored by fluorimetry. Previous studies have established that increases in NADH fluorescence accurately reflect the impairment in oxidative phosphorylation which occurs during brief periods of acute hypoxia. However, the potential usefulness of fluorimetry for following longer, clinically relevant periods of ischemia has not been explored. We studied changes in NADH fluorescence in rat hepatocyte suspensions and in isolated-buffer-perfused rat livers during hypoxia (pO2 < 50 mm Hg) for periods as long as 180 min. NADH fluorescence of hepatocyte suspensions consistently increased by about 15% after 13 to 15 min of hypoxia and coincided with a marked decrease in tissue ATP levels. Reoxygenation after 15 or 30 min of hypoxia resulted in recovery of ATP and NADH with minimal loss of viability, as measured by trypan blue exclusion. After 60 to 180 min hypoxia, the initial increase in NADH fluorescence was followed by a progressive, irreversible decline which correlated with decreased cell viability. Similar changes in NADH fluorescence were observed in isolated-perfused rat livers in which NADH fluorescence was monitored at the liver surface with a fiberoptic probe. Hypoxia for 30 min had no effect on NADH fluorescence, but hypoxia for longer periods caused a steady increase in fluorescence after 45-60 min. When hypoxia was prolonged (120 or 180 min), fluorescence peaked after 60-75 min and then declined progressively to levels below baseline. The greatest decrease in fluorescence was seen after 180 min of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Use of a chlorhexidine dressing to reduce microbial colonization of epidural catheters.

We performed a prospective randomized controlled trial to assess the efficacy of a chlorhexidine dressing in reducing the microbial flora at the insertion site of epidural catheters. These catheters were used for acute pain management and were dressed either by a standardized method or with a CHX/urethane sponge composite. Microbial colonization of the catheter developed in 9 of 31 controls (29.0%) and 1 of 26 (3.8%) catheters with the CHX dressing (P less than 0.05%). The CHX dressing caused no adverse effects. The data suggest that delivery of antiseptic to the catheter wound site reduces catheter colonization with a possible reduction in the risk of epidural catheter-related infection.

Analgesia, Epidural↗
PubMed1988

An attachable silver-impregnated cuff for prevention of infection with central venous catheters: a prospective randomized multicenter trial.

PURPOSE: Percutaneously inserted central venous catheters are widely used. Catheter-related bacteremia or fungemia is the most frequent serious complication of these catheters. In an attempt to reduce the frequency of such infections, a subcutaneous cuff constructed of a biodegradable collagen matrix impregnated with bactericidal silver was developed. Our goal was to assess, in a multicenter clinical trial, the effectiveness of this cuff in preventing catheter-related infection. MATERIALS AND METHODS: Central venous catheters needed for fluid or drug therapy, hemodynamic monitoring, or hyperalimentation in patients in three centers were randomly assigned to be inserted with or without the cuff. Patients and catheters in the two groups were comparable in terms of risk factors predisposing to infection, including colonization of skin about the insertion site. RESULTS: The results with 234 catheters inserted into a new site showed that catheters inserted with the cuff were threefold less likely to be colonized on removal (more than 15 colony-forming units) than were control catheters (28.9 percent versus 9.1 percent, p = 0.002) and were nearly fourfold less likely to produce bacteremia (3.7 percent versus 1.0 percent). Adverse effects from the cuff were not seen. The cuff did not confer protection, however against infection with catheters inserted over a guidewire into old sites. Most of the catheter-related infections identified in this study, including four of the six bacteremias, appear to have been caused by microorganisms colonizing skin about the insertion site, affirming the pathogenetic basis for benefit seen with the cuff in this clinical trial; two may have derived from contamination of the catheter hub. CONCLUSION: This novel, silver-impregnated, attachable cuff can substantially reduce the incidence of catheter-related infection with most percutaneously inserted central venous catheters, can extend the time catheters can be left in place safely, and can prove cost-beneficial.

Adult↗
PubMed1987

Leukotriene D4 increases extravascular lung water in the dog.

The peptide leukotrienes have been detected in animals that have received endotoxin injections and also have been associated with patients suffering from the adult respiratory distress syndrome (ARDS). The ability of leukotriene D4 (LTD4) to cause pulmonary capillary permeability changes was investigated in ten anesthetized mongrel dogs. Four dogs were used as controls and six dogs received intravenous LTD4 (0.25 microgram/kg). There was a variable response in that two treated animals showed no apparent effect of LTD4. Analysis of the results from the remaining four treated animals demonstrated a significant increase in extravascular lung water (EVLW) that peaked 3 hr after LTD4 from 5.4 +/- 0.6 to 10.3 +/- 0.5 ml/kg (P less than .01). In these four dogs, EVLW increased before slight, but statistically significant, rises in pulmonary artery wedge pressure (4 +/- 1 to 9 +/- 1 mm Hg, P less than .01) and mean pulmonary artery pressure (13 +/- 1 to 17 +/- 1 mm Hg, P less than .01) occurred. During the same period, cardiac output decreased 56 +/- 7% (P less than .01), but no change in airway resistance was observed. This study is the first in vivo demonstration that LTD4 directly alters pulmonary fluid balance in the dog. We conclude LTD4 can cause increases in EVLW and may be an important mediator of the permeability changes observed in various clinical events that lead to the adult respiratory distress syndrome.

Animals↗
PubMed1986

Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.

Animals↗