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Biomedical subjects

D W Gump

Publications and source records attributed to D W Gump.

At least 19 recordsLinked to original sources

Evidence that bismuth salts reduce invasion of epithelial cells by enteroinvasive bacteria.

The effects of sublethal concentrations of bismuth salts on bacterial invasion of mammalian cells were investigated. Pepto-Bismol, bismuth subsalicylate, and bismuth oxychloride, produced by interacting bismuth subsalicylate and simulated gastric juice, in suspension at concentrations as low as 1.4 mM significantly interfered with the invasion of RPMI-4788 cells by two different strains of Yersinia enterocolitica. Invasion of the mammalian epithelial cells by other enteric bacteria was also reduced significantly by some of these bismuth salts. Commercially obtained bismuth oxychloride, bismuth sulfide, and sodium salicylate had no affect on invasion by Y. enterocolitica. Exposure of Y. enterocolitica 8081c to Pepto-Bismol for as brief a time as 5 min was sufficient to produce the inhibitory effect. Removal of bismuth bound to bacteria by sodium potassium tartrate did not reverse the inhibition. Electron-dense deposits are observed in Y. enterocolitica 8081c exposed to bismuth subsalicylate, suggesting that interference of invasion may result from bismuth permeation of the bacterial cell wall.

Bacteria

Deposition of bismuth by Yersinia enterocolitica.

Yersinia enterocolitica 8081c cultures in exponential growth were incubated for 1 h in 0.1% microcrystalline bismuth subsalicylate (BSS) suspensions. Scanning electron microscopy (SEM) revealed microcrystals directly bound to BSS-treated bacteria. Energy dispersive spectroscopy (EDS) X-ray microanalysis of the attached microcrystals confirmed that the crystals were the microcrystalline BSS. X-ray spectra positive for bismuth were also obtained by SEM-EDS X-ray microanalysis of whole bacteria, suggesting metal incorporation into the bacteria in regions absent of bound microcrystals. Transmission electron microscopy of thin sections of embedded preparations of BSS-treated exponential-growth-phase bacteria showed electron-dense deposits in the periphery of the bacteria. Y. enterocolitica cultures that were in stationary phase at the time of incubation with microcrystalline BSS showed no evidence of the electron-dense deposits and EDS spectra were negative for bismuth. Bacteria incubated in the absence of microcrystalline BSS also lacked electron-dense deposits. Scanning transmission electron microscopy used in conjunction with EDS X-ray microanalysis to view and analyze semi-thick sections (250-300 nm) of embedded preparations of BSS-treated bacteria in exponential growth confirmed that the electron-dense deposits at the periphery of the bacteria are the sites of bismuth depositions.

Bismuth

Activity of 2,4-diaminoquinazoline compounds against Candida species.

Forty recent clinical isolates of three different Candida sp. were tested in the microtiter system for susceptibility to two new 2,4-diaminoquinazoline (DAQ) compounds, amphotericin B and flucytosine. The two DAQ preparations showed activity similar to amphotericin B and flucytosine. The geometric mean minimal inhibitory concentrations for these four drugs were as follows: DAQ 1A, 0.64 mug/ml; DAQ 2A, 1.39 mug/ml; amphotericin B, 1.03 mug/ml; and flucytosine, 0.72 mug/ml. An additional seven DAQ compounds were tested but showed less or no activity against 17 Candida isolates. Forty-eight-hour viability studies with DAQ 2A alone or in combination with amphotericin B, flucytosine, or sulfamethoxazole were carried out with one isolate of intermediate susceptibility to each of these agents except sulfamethoxazole. For this isolate the combination of DAQ 2A and sulfamethoxazole was synergistic, and the combination of DAQ 2A and AMB was either synergistic or additive, whereas the combination of DAQ 2A and flucytosine was antagonistic. Although regrowth of cultures exposed to DAQ 2A was noted over a 48-h period, neither degradation of the drug nor development of resistance to the drug could be detected. Swiss white mice receiving DAQ 1A at a dose of 6 mg/kg for 5 days showed no obvious signs of toxicity, including weight loss.

Amphotericin B

Farmer's lung disease in Vermont.

Several Vermont population groups were surveyed for the occurrence of antibodies to thermophilic actinomycetes. Antibodies to M. faeni and T. vulgaris were measured by the precipitin method in all subjects and, in 124 subjects, M. faeni antibodies were also measured by the indirect fluorescent antibody (IFA) technique. There was relatively good correlation between the two techniques (r 0.48, p less than 0.01). Hospital employees, blood donors and patients with chronic bronchitis were generally negative for precipitins to thermophilic actinomycetes. Of the 258 Vermont dairy farmers surveyed, 14 (5.4%) had precipitins to M. faeni, 3 (1.2%) had precipitins to T. vulgaris but only 1 farmer with antibodies to M. faeni had symptoms of possible farmer's lung disease (FLD). On the other hand, 10 (4.1%) precipitin-negative farmers had symptoms possibly consistent with FLD. The IFA test did not correlate any better with symptoms. 7 (5.6%) patients with pulmonary fibrosis had precipitins to M. faeni 5 of these were diagnosed as having FLD. 18 (14.4%) had precipitins to T. vulgaris and only 3 of these patients were felt to have hypersensitivity pneumonitis. Patients with pulmonary fibrosis and FLD hat IFA titers of greater than or equal to 1/128, but so did asymptomatic farmers.

Adolescent

Legionnaires' disease in patients with associated serious disease.

Of nine patients with Legionnaires' disease, seven were receiving corticosteroids, and all nine had serious underlying diseases. Direct immunofluorescent examination of respiratory secretions, including sputum and transtracheal aspirates, showed the Legionnaires' disease (LD) bacterium in five of seven patients who seroconverted and in a sixth patient with a single elevated titer to the LD bacterium. All nine patients received erythromycin therapy, and five survived. Two patients showed persistence of their infection after receiving 2 weeks of erythromycin therapy, and two patients developed pulmonary abscesses. These cases of Legionnaires' disease show the occurrence of pulmonary abscesses, the possibility of relapse after giving only 2 weeks of erythromycin therapy, and the utility of direct immunofluorescence for early diagnosis.

Adrenal Cortex Hormones

The protective effect of intraperitoneal splenic autotransplants in mice exposed to an aerosolized suspension of type III Streptococcus pneumoniae.

Splenosis has been shown to occur after traumatic injury to the spleen. It is postulated that this is the mechanism for the low incidence of bacterial infection in this group of patients when compared to those who undergo splenectomy for other reasons. Therefore, we studied the effect of exposure to an aerosolized suspension of type III Streptococcus pneumoniae on splenectomized mice who had either all or half of their splenic tissue cut up and reimplanted into the abdominal cavity 8 wk prior to bacterial exposure. It was determined that the mortality experience of these two groups of mice was similar to each other and no different from the sham control group, although all three groups had a statistically significant lower mortality experience than the splenectomized control group. This study demonstrates that splenosis in mice can protect against aerosolized bacterial infection.

Animals

Chloramphenicol: an impatient study of use and abuse.

During a six-month period, chloramphenicol was administered systemically to 100 patients and topically to 24 patients who were admitted to the Medical Center Hospital of Vermont, Burlington, Vermont. Seventy-nine percent of the patients receiving the drug systemically were on surgical services, 13% were on the pediatric service, and 8% were on the medical service. In this group, chloramphenicol was administered appropriately in 60.4% of cases as follows: 57.5% on the surgical, 50% on the medical, and 84.6% on the pediatric services. In 19 of 35 instances of inappropriate use on the surgical services, a potentially less toxic antibiotic could have been chosen. Eight cases were treated inappropriately because of dosage errors, and in seven cases no antibiotic should have been used. On the medical services all inappropriate use was due to underdosage, and on the pediatric service there was one case of incorrect dosage and one instance in which a less toxic antibiotic could have been chosen. Ophthalmological use of the drug accounted for all topical use. Of 24 patients treated, 21 received the drug for prophylaxis and three for therapy.

Child

Cytomegalovirus encephalitis in immunologically normal adults. Successful treatment with vidarabine.

Acute cytomegalovirus (CMV) encephalitis developed in two immunologically normal adults. The diagnosis was confirmed by isolation of CMV from the CSF and urine in one case and from temporal lobe biopsy tissue, CSF, and urine in the second case. Both patients were treated with vidarabine and showed dramatic clinical improvement. Virus excretion, which had been chronic in one case, cleared after therapy. To our knowledge, these are the first persons with CMV encephalitis evidenced by isolation of the virus from the CNS. The response to vidarabine was impressive and warrants further evaluation.

Acute Disease

Side effects of minocycline: a double-blind study.

We studied the incidence and type of side effects of minocycline in a double-blind study. A total of 45 volunteers (18 men and 27 women) were given minocycline, and 44 volunteers (23 men and 21 women) were given placebo. The men in both the minocycline and placebo groups were significantly (P < 0.0001) larger than the women in the comparable groups. Minocycline dosage was 100 mg every 12 h for 5 days, and placebo was administered in an identical manner. Minocycline serum concentrations were determined in 12 volunteers at 1, 2, 4, and 6 h after the morning doses on days 1, 3, and 5 of the study. Side effects were recorded by volunteers in diaries and also through daily interviews and were evaluated by examination and electronystagmography. Peak minocycline serum concentrations were seen by day 3 and correlated with the peak onset of side effects. These concentrations were significantly higher in women than in men. Vestibular side effects occurred in 70.4% of the women on minocycline and significantly (P < 0.0001) exceeded the rate of the women on placebo (9.5%). Only loss of balance was significantly (P < 0.05) increased in the men taking minocycline as contrasted with men on placebo. Electronystagmography generally revealed no abnormalities. Side effects were usually not severe: four volunteers in the minocycline group and two in the placebo group discontinued their capsules because of side effects. It is concluded that women experience an unacceptably high incidence of side effects from minocycline, and this may be related to their higher serum concentrations, which in turn may relate to their smaller size.

Clinical Trials as Topic

Side effects of minocycline: different dosage regimens.

The incidence of side effects due to two dosage regimens of minocycline was examined over a 5-day period. A total of 60 normal women volunteers were randomly assigned in a double-blind manner to either a group who took 100 mg of minocycline twice a day or a group who took 75 mg of minocycline twice a day for 5 days. Both groups were comparable from the standpoints of age, size, race, and the use of oral contraception, nicotine, and ethanol. They were seen on a daily basis, and symptoms were evaluated by both volunteers (from diaries) and physicians. Minocycline serum concentrations were determined on blood samples taken 2 h after the a.m. dose. Volunteers taking 150 mg of minocycline per day had significantly lower serum antibiotic concentrations than those taking 200 mg per day. However, both low- and high-dose groups exhibited similar incidence and prevalence of recorded symptoms, with the single exception of nausea, where the low-dose group had fewer symptoms than the high-dose group (P = 0.035). Symptomatic volunteers did not have higher serum concentrations of minocycline than their asymptomatic counterparts. When either weight or surface area was examined with antibiotic serum concentration there was a significant inverse correlation between the two on day 2 for both groups and also on day 4 for the low-dose group. It is concluded that, in women, a dose of 150 mg of minocycline per day is associated with the same degree of side effects as a dose of 200 mg per day.

Adolescent

Vidarabine therapy for severe herpesvirus infections. An unusual syndrome of chronic varicella and transient immunologic deficiency.

Six patients with severe herpesvirus infections were successfully treated with vidarabine. One patient had a previously undescribed syndrome of chronic cutaneous varicella infection of eight months' duration, associated with transient but complete duppression of lymphocyte response to conconavalin A. Other diagnoses were severe varicella pneumonia, progressive cytomegalovirus pneumonia associated with acute lymphocytic leukemia, herpes simplex encephalitis, severe zoster associated with stage IV lymphoma, and disseminated herpes simplex in a patient receiving high doses of steroids. All patients showed cessation of new lesions or abrupt clinical improvement between days 2 and 4 after initiation of therapy, and all were cured of their clinical infection. Dramatic improvement in all of our patients and the minimal toxicity observed make vidarabine suitable for use in severe herpesvirus infections.

Adolescent

Severe Mycoplasma pneumoniae pneumonia.

Four cases of severe Mycoplasma pneumoniae infection are reported which were treated in a single hospital over the course of 4 years. The difficulties in the diagnosis of M. pneumoniae infections are eminently demonstrated by these cases. Because of the fact that it generally takes 2-o weeks to make this diagnosis, the physician must utilize clues of limited reliability. If gram stains and culture of sputum fail to demonstrate any bacterial pathogen and the patient has a chest X-ray compatible with this diagnosis as well as a white blood count less than 15,000/mm3, M. pneumoniae infection may be present. A good antimicrobial choice in such a situation is erythromycin.

Adolescent