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Biomedical subjects

S D Nightingale

Publications and source records attributed to S D Nightingale.

At least 37 records · Page 2Linked to original sources
PubMed1992

Sustained-release ganciclovir therapy for treatment of cytomegalovirus retinitis. Use of an intravitreal device.

A surgically implantable device for sustained intravitreal release of ganciclovir has been developed. The device delivers ganciclovir intraocularly over approximately 4 to 5 months. Eight patients with acquired immunodeficiency syndrome (AIDS) and associated cytomegalovirus (CMV) retinitis were recruited as part of a phase 1 study. Thirteen eyes with active CMV retinitis underwent surgical implantation of the ganciclovir device. All eyes showed resolution of the CMV retinitis; none showed progression. Visual acuity remained unchanged in three eyes, improved in six eyes, and decreased in four eyes. Surgical complications included mild vitreous hemorrhage, astigmatism, and suprachoroidal placement of the device. Retinal detachment occurred in three eyes as the retinitis resolved. This new intraocular drug delivery system offers many advantages compared with intravenous therapy or repeated intravitreal ganciclovir injections for the management of CMV retinitis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Intravitreal ganciclovir pharmacokinetics in rabbits and man.

Cytomegalovirus (CMV) retinitis occurs in immunocompromised patients and can be treated by repeated intravenous or intravitreal injections of ganciclovir (GCV) or foscarnet. Due to toxicity and complications these modalities are not ideal. The development of alternative administration routes is hindered by a lack of pharmacokinetic data. Devices giving pseudo zero order release of GCV were implanted intravitreally first in rabbits and then in patients with AIDS associated CMV retinitis as part of a Phase I clinical trial. Steady state intravitreal GCV levels were obtained immediately after death and the elimination rate constants were calculated assuming first order pharmacokinetics. Normalizing for retinal surface area, distribution volume and anatomic volume, the retinal elimination rate constants were calculated. These were found to be 0.017 cm-2hr-1 in rabbits and 0.015 cm-2hr-1 in man. This indicates that the rabbit eye is a good model for studying intravitreal pharmacokinetics of ganciclovir and suggests a common elimination mechanism which may be trans-retinal.

Animals↗
PubMed1992

Monoclonal antibody to Pneumocystis carinii. Comparison with silver stain in bronchial lavage specimens.

Monoclonal 3F6 anti-Pneumocystis carinii antibody (MAB-3F6) was used to stain cell blocks from 164 bronchial lavage specimens from patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex and compared with slides stained with Grocott's modification of the Gomori methenamine silver stain. Pneumocystis organisms were present in 83 of 164 cases using MAB-3F6 stain, whereas Grocott's modified silver stain demonstrated Pneumocystis organisms in 48. MAB-3F6 demonstrated Pneumocystis organisms in 38 cases with negative silver stains, whereas silver stain identified Pneumocystis organisms in only three MAB-3F6-negative cases. Of 70 patients with clinical Pneumocystis pneumonia at the time of the specimen was obtained, 59 had MAB-3F6-positive specimens, whereas 39 had organisms detected using Grocott's modified silver stain. Of 37 patients without clinically apparent Pneumocystis pneumonia any time in their course, 4 had abundant organisms and 33 had negative stains with MAB-3F6. MAB-3F6 detected Pneumocystis organisms in 22 of 31 cases of Pneumocystis pneumonia that had no organisms identified using Grocott's silver stain (X2 = 5.76, P = 0.016). MAB-3F6 immunochemical staining is a more sensitive method than Grocott's modified silver stain to detect Pneumocystis organisms.

Antibodies, Monoclonal↗
PubMed1992

Incidence of Mycobacterium avium-intracellulare complex bacteremia in human immunodeficiency virus-positive patients.

The product-limit incidence of Mycobacterium avium-intracellulare complex (MAC) bacteremia in 1006 human immunodeficiency virus (HIV)-positive patients followed at one institution over a 3-year period from the day of AIDS diagnosis with monthly lysis-centrifugation blood cultures was 21% +/- 2% SE at 1 year and 43% +/- 3% at 2 years. The product-limit incidence of MAC bacteremia at 1 year after the patients' first CD4 cell count was related to both the CD4 cell count and to whether they had an AIDS diagnosis (both P less than .0001) but not to age, sex, or race. This incidence was 39% +/- 6% for CD4 cell counts of less than 10/mm3, 30% +/- 5% for 10-19/mm3, 20% +/- 4% for 20-39/mm3, 15% +/- 4% for 40-59/mm3, 8% +/- 3% for 60-99/mm3, and 3% +/- 1% for 100-199/mm3. MAC may eventually infect most if not all HIV-positive patients who do not die from another HIV-related event.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Primary prophylaxis with fluconazole against systemic fungal infections in HIV-positive patients.

OBJECTIVE: To investigate the efficacy of fluconazole prophylaxis against systemic fungal infections in HIV-positive patients. DESIGN: Open label treatment compared with historical controls. SETTING: Patients were seen at the Parkland Memorial Hospital HIV Clinic, Dallas, Texas, USA between 1 March 1990 and 28 February 1991. PATIENTS, PARTICIPANTS: Three hundred and thirty-seven historical controls were followed for 157 patient-years, and 329 fluconazole-treated patients for 145 patient-years. INTERVENTIONS: Fluconazole (100 mg daily) was administered to all patients with CD4 lymphocyte counts less than 68 x 10(6)/l seen at our HIV clinic after 1 March 1990. MAIN OUTCOME MEASURES: Lysis-centrifugation blood cultures were recorded monthly for all patients during both study periods. RESULTS: Twenty infections (16 cryptococcosis, four histoplasmosis) occurred in 337 historical reference control patients (product-limit 1-year incidence, 7.5 +/- 2.0/year). Four infections (one cryptococcosis, three histoplasmosis) occurred in the treated patient group (product-limit 1-year incidence, 1.8 +/- 0.9/year). CONCLUSIONS: Fluconazole warrants further evaluation for prophylaxis against systemic fungal infections in HIV-positive patients.

Adult↗
PubMed1990

Disseminated histoplasmosis in patients with AIDS.

Disseminated histoplasmosis was diagnosed in 36 (4%) of 980 patients with AIDS seen at Parkland Memorial Hospital in Dallas, Texas before September 30, 1989. Diagnostic sensitivity of blood culture plus examination of peripheral smear was 88%; sensitivity of bone marrow aspiration and blood culture was 80%. Median CD4 lymphocyte count at diagnosis was 33/cu mm. Median actuarial survival from the date histoplasmosis was diagnosed was 188 days. Thirteen (36%) of the 36 patients died before adequate antifungal therapy could be administered, while 13 survived long enough to receive 1,500 mg of amphotericin B; actuarial survival of the latter group from the date 1,500 mg of amphotericin B had been infused was 47% at 1 year. The substantial early mortality of AIDS-associated disseminated histoplasmosis and the modestly encouraging survival of those who were diagnosed in time to receive adequate therapy raise the issues of surveillance, prophylaxis, and empiric therapy for this infection in selected HIV-positive patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Risk preference and decision making in critical care situations.

Physician attitudes towards risk may influence their behavior in critical care situations. To explore this hypothesis, physicians' responses to a questionnaire about risk were compared to their preferences towards "intubation" or "current therapy without intubation" for a hypothetical patient with end-stage lung disease, and to the length of time they performed cardiopulmonary resuscitation before they declared their efforts unsuccessful. When the choices on the questionnaire were framed in terms of loss, choice of the risky alternative was associated with greater preference for "intubation," and with longer duration of resuscitation efforts (both p less than .005). At least part of the variation in physician attitudes and practices towards the care of the critically or terminally ill is associated with measurable psychologic differences among individual physicians.

Adult↗
PubMed1981

A shared cryoglobulin antigen in familial cryoglobulinemia.

Ten members of 3 generations of a family have IgM-IgG cryoglobulins and rheumatoid factors in their sera; one additional member has rheumatoid factor but not cryoglobulins. The disorder occurs in an autosomal dominant pattern. Here we describe an antigen, first identified on the cryoglobulin IgM of the index case, which is present in the sera of all 11 members of this kindred with rheumatoid factor. This antigen has the serologic properties of an IgM rheumatoid factor idiotype.

Agglutination Tests↗
PubMed1981

Inheritance of mixed cryoglobulinemia.

This paper describes a family in which 10 members of 3 generations have IgM-IgG cryoglobulinemia. Their pedigree is characteristic of autosomal dominant inheritance. No underlying disease that could account for the cryoglobulinemia has been identified in any patient, and no linkage of the cryoglobulinemia to HLA-A and -B locus haplotypes, blood group antigens, or immunoglobulin Gm allotypes has been detected. The rheumatoid factors of this kindred react with some, but not all, human IgG; however, their rheumatoid factors are not antibodies to any known human Gm or Km allotype. This family demonstrates that "essential" mixed cryoglobulinemia can be inherited, and that the clinical manifestations of an inherited cryoglobulinemia may vary among family members.

ABO Blood-Group System↗
PubMed1978

Glucose-induced hyperkalemia with normal aldosterone levels. Studies in a patient with diabetes mellitus.

A diabetic patient exhibited glucose-induced hyperkalemia despite normal plasma and urinary aldosterone levels. The patient received no diuretics, was not acidotic, and had a creatinine clearance of 39 ml/min. Insulin or pharmacologic doses of desoxycorticosterone acetate eliminated the glucose-induced hyperkalemia. Normal aldosterone levels may be insufficient to protect certain diabetic patients from glucose-induced hyperkalemia.

Aged↗
PubMed1975

Pharmacokinetic characteristics of doxycycline accumulation in normal and severely diseased kidneys.

Intrarenal concentrations of doxycycline were measured in 48 normal canine kidneys during wide variations in urine pH and the systemic state of hydration of the experimental animals. The results were compared with the renal parenchymal levels achieved in 10 severely diseased human kidneys. Although the state of hydration, the urine pH, and renal disease all significantly influenced the urinary concentrations and rate of renal clearance of doxycycline, there was no detectable difference between concentrations in normal renal tissue and those in severely diseased kidneys. This result is in contradistinction of the findings for previously evaluated antibiotics. The levels of doxycycline measured in renal tissue averaged twice the concentration in serum without notable difference among levels in renal cortex, medulla, and papilla. Prospective clinical trials will be necessary for identification of any solid correlation between the remarkable characteristics of accumulation of doxycycline in diseased renal parenchymal tissue and the clinical, therapeutic importance of such an observation.

Animals↗
PubMedDate not supplied

Prophylaxis against Mycobacterium avium-intracellulare complex infections in human immunodeficiency virus-infected patients.

Infection due to the Mycobacterium avium complex (MAC) accounts for the most frequent AIDS-related opportunistic infections, but MAC infection is usually not the first AIDS-defining event that a patient infected with HIV experiences. The incidence increases linearly over time, at a rate of 20 to 25% per year, after a patient's first AIDS-defining event, and the incidence increases exponentially as the CD4+ cell count approaches zero. There is evidence that MAC may eventually infect most if not all HIV-infected patients who do not die from another HIV-related event. Since MAC infection contributes substantially to the morbidity and mortality of AIDS patients, prophylaxis appears to be mandatory. Rifabutin was the first drug which was shown to be effective in preventing MAC infection, and, recently, prophylaxis with clarithromycin was also found to prevent the disease. The optimal approach to prophylaxis still needs to be defined. Since a large majority of MAC infections occur in patients with CD4+ cell counts below 50/microliter, recommendations regarding the prophylaxis of patients with a history of an AIDS-defining opportunistic event and a CD4+ cell count between 50 and 200/microliter can be individualized, depending for example on how well the patient seems to be responding to antiretroviral treatment. Prophylaxis against MAC should be provided for any HIV-infected patient with a CD4+ cell count less than 50/microliter.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Risk preference and laboratory test selection.

The risk preferences in situations of potential gain, and of potential loss, expressed by 67 physicians were correlated with the numbers of laboratory tests they selected after review of identical copies of two outpatient charts. Physicians who chose a 50/50 gamble of losing ten or no years of life expectancy over an equivalent certain loss of five years selected twice as many tests as those who chose the loss (p less than 0.025). Risk preferences may provide some insight into why some physicians order more laboratory tests than do others.

Decision Theory↗