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Biomedical subjects

J L Ho

Publications and source records attributed to J L Ho.

51 records · Page 3Linked to original sources

Inhibition of macrophage secretion by tetanus toxin is not directly linked to cytosolic calcium homeostasis.

Tetanus toxin (TT) inhibits secretion of neurotransmitters from neurons and lysozyme from human macrophages (Mphi). Because these secretory events are associated with changes in cytosolic free calcium [Ca2+]i, we examined the effect of TT on Mphi calcium homeostasis and secretion in response to ionomycin and phorbol myristate acetate (PMA). Using Quin 2 to report [Ca2+]i, basal [Ca2]i was similar for control cells (133 nM) and Mphi treated with TT (127 nM). In response to ionomycin (50 nM) [Ca2+]i increased to 548 +/- 74 nM in control cells and to 357 +/- 36 nM in TT-treated Mphi (p less than 0.02, N = 12). Despite this rise in [Ca2+]i, neither control Mphi nor TT-treated Mphis secreted the lysosomal enzyme lysozyme in response to this concentration of ionomycin (50 nM). In both control and TT-treated Mphi, stimulation with a higher concentration of ionomycin (1000 nM) caused saturation of the quin 2 fluorescence signal. However, lysozyme secretion from TT-Mphi was inhibited. In response to the phorbol ester, PMA (3 uM), [Ca2+]i did not increase in either control Mphi or TT-treated Mphi. However, secretion of lysozyme from TT-treated Mphi was also inhibited in response to this stimulus (70.8% of control, p less than 0.02, N = 3). These data indicate that the ability of TT to inhibit secretion from Mphi is not directly linked to alterations of cytosolic calcium homeostasis.

Aminoquinolines↗

In vitro evaluation of clindamycin in combination with oxacillin, rifampin, or vancomycin against Staphylococcus aureus.

In a study of antibiotic combinations of clindamycin with rifampin, oxacillin, or vancomycin using the time kill-curve method, the combination of clindamycin and rifampin were sometimes synergistic (5 of 15 times), otherwise indifferent and always enhanced killing of fifteen tested Staphylococcus aureus isolates. In contrast, vancomycin and clindamycin or oxacillin and clindamycin were either indifferent or antagonistic (approximately 50%). Vancomycin alone, however, was generally as effective as the combinations of clindamycin and rifampin.

Clindamycin↗

Randomized prospective study comparing moxalactam and cefoxitin with or without tobramycin for the treatment of serious surgical infections.

The efficacy and toxicity of moxalactam were compared with the efficacy and toxicity of cefoxitin given with or without tobramycin to 109 patients with surgical infections. A total of 66 patients could be assessed for efficacy (33 patients in each group); 13 of the cefoxitin-treated patients also received tobramycin for at least 72 h. Most patients had intraabdominal infections; 17 had peritonitis, 14 had intraabdominal abscesses, and 7 had perforation of a gangrenous appendix. There were 15 patients with necrotizing soft-tissue infections. The predominant pathogens were members of the Enterobacteriaceae and Bacteroides fragilis. The cure rates were 79% (26 of 33 patients) for moxalactam and 88% (29 of 33 patients) for cefoxitin; the difference in cure rates was not statistically significant. In several patients, cultures of purulent intraabdominal exudates were negative, although bacteria were observed after Gram staining; this presumably reflected the potent activity of the antibiotic therapy which had been started before surgical drainage could be carried out. Adverse effects were observed in 18 of 44 assessable patients (41%) in the cefoxitin group and in 12 of 36 patients (33%) in the moxalactam group; the difference in the rates of adverse effects was not statistically significant. Our results suggest that moxalactam is similar in efficacy and toxicity to cefoxitin given with or without tobramycin for the treatment of serious surgical sepsis caused by a mixture of anaerobic and aerobic pathogens.

Adolescent↗

An outbreak of type 4b Listeria monocytogenes infection involving patients from eight Boston hospitals.

During September and October 1979, 23 patients admitted to hospitals in the Boston area had systemic Listeria monocytogenes infection. Twenty (87%) of these isolates were L monocytogenes type 4b, whereas only nine (33%) of the isolates serotyped during the preceding 26 months had been 4b. Patients with type 4b Listeria infection during the epidemic period (case patients) differed from patients with sporadic Listeria infection in the preceding two years in that more of the case patients had hospital-acquired infection (15/20 vs 4/18), had received antacids or cimetidine before the onset of listeriosis (12/20 vs 3/18), and had gastrointestinal tract symptoms that began at the same time as fever (17/20 vs 4/18). In addition, more case patients took antacids or cimetidine compared with patients matched for age, sex, and date of hospitalization (12/20 vs 10/40). Three foods were preferred by case patients more frequently than by control patients: tuna fish, chicken salad, and cheese. However, the only common feature appeared to be the serving of these foods with raw celery, tomatoes, and lettuce. The raw vegetables may have been contaminated with Listeria, which was able to survive ingestion because of gastric acid neutralization and subsequently to cause enteritis, bacteremia, and meningitis in susceptible hosts. However, we cannot exclude pasteurized milk as a source of this outbreak.

Aged↗

Potable water as a source of Legionnaires' disease.

A three-year epidemic of legionnaires' disease in a hospital was dramatically curtailed following hyperchlorination of the potable water supply. The hypothesis that potable water was the source for the outbreak was further supported by isolation of Legionella pneumophila (the agent of legionnaires' disease) from the hospital water supply, observation that a sudden upsurge had occurred in the number of cases following a peculiar manipulation of the hospital water system, and documentation of a 30-fold increase in concentration of organisms in the water when this manipulation was artificially recreated. Thus, potable water may be an important source of epidemic legionnaires' disease and continuous hyperchlorination a method of control.

Adult↗

Tetanus toxin inhibits secretion of lysosomal contents from human macrophages.

The mechanism by which tetanus toxin (TT) inhibits the release of neurotransmitters from neurons is unknown. Since secretion of lysosomal contents from monocytes/macrophages (MOs) appears to be similar to the release of synaptosomal contents from neural cells, we examined the effects of TT on MO secretion. Adherent human MOs were cultured overnight with or without TT (1.25 micrograms/ml), washed, and resuspended in TT-free medium. In response to the calcium ionophore A23187, TT-treated MOs secreted significantly less lysozyme (27.2% +/- 3.2%) than did control cells (48.6% +/- 6.8%; 44.1% inhibition, P less than .001). TT inhibition of A23187-stimulated release of lysozyme from MOs was dose dependent, and higher concentrations of A23187 could not overcome the inhibitory effect of TT. MO secretions in response to a second secretagogue, phorbol myristate acetate, was also inhibited by TT. Heated TT (100 C for 1 hr), which has no in vivo toxicity, also failed to inhibit MO secretion. The inhibition of secretion by TT required holotoxin. C- and B-fragments produced no appreciable effect on secretion in response to either secretagogue. These studies indicate that human MOs may be a readily accessible, model system for the study of the biochemical basis of TT intoxication. However, observations in this system must be confirmed in neurons, the natural site of TT intoxication.

Calcimycin↗

Hemophilus aphrophilus osteomyelitis.

Hemophilus aphrophilus is a slow-growing, aerobic (capnophilic), gram-negative bacillus. H. aphrophilus was the cause of hematogenous vertebral osteomyelitis in a patient who had a lip laceration. This was successfully treated with parenteral penicillin. The antimicrobial susceptibilities of 14 antimicrobial agents are presented.

Adult↗

Acquired immunodeficiency syndrome with progressive multifocal leukoencephalopathy and monoclonal B-cell proliferation.

A 34-year-old man who used intravenous drugs developed the acquired immunodeficiency syndrome with lymphadenopathy, Mycobacterium tuberculosis pneumonia, and progressive multifocal leukoencephalopathy. Early biopsy specimens of the lymph node showed hyperplasia without evidence of lymphoma. Later, immunologic analysis of peripheral blood lymphocytes showed inversion of the helper/suppressor T-lymphocyte ratio and persistent monoclonal B-cell proliferation without clinically overt lymphoma. The clinical course of this patient suggests that abnormal immune responses seen in the setting of the acquired immunodeficiency syndrome may evolve into lymphoproliferative disorders detectable by peripheral blood lymphocyte analysis.

Acquired Immunodeficiency Syndrome↗

Recurrent urban histoplasmosis, Indianapolis, Indiana, 1980-1981.

In January 1981, informal surveillance of acute histoplasmosis in Indianapolis, Indiana, revealed a marked increase in disease activity for the last quarter of 1980. Fifty-one patients with onset of acute histoplasmosis during this period were identified through review of hospital admissions, emergency room visits, and serologic records at Indianapolis hospitals and the Indiana State Board of Health. In a retrospective case-control study, the authors found a significant association between developing acute histoplasmosis during this period and working or attending classes in a 2 sq mi (5.2 sq km) area encompassing the Indiana University-Purdue University campus (p = 0.015, Fisher's exact test). A review of construction activities on or near the campus during the epidemic period suggested that the probable source of infection was excavation activity for a large new indoor swimming complex (natatorium). Skin tests and serosurveys of students on campus by a newly developed radioimmunoassay for histoplasmal immunoglobulin M antibodies supported the association of infection with exposure to this site (p less than 0.05).

Disease Outbreaks↗

Streptococcal wound infections caused by a vaginal carrier.

During a four-month period, ten cases of group A streptococcal (GAS) postoperative wound infection occurred among patients in a community hospital. Bacteremia developed in two patients, and one patient died. Group A streptococcal surgical wound infections were associated with exposure to a circulating nurse and duration of surgery. Prophylactic antibiotic reduced the risk of infection. Vaginal, perineal, and anal cultures from nurse A yielded GAS, serotype M-4, T-4, as did the blood of two infected patients. Penicillin eradicated GAS colonization of nurse A, and she returned to work. Five months later, two additional cases of GAS postoperative wound infections occurred and were associated with recolonization of the same nurse with GAS, serotype M-nontypeable, T-12. She was relieved of patient-care duties, and no further cases have occurred.

Anal Canal↗

High pressure liquid chromatographic-thermal energy determination of N-nitrosodiethanolamine in cosmetics.

Methods for the determination and confirmation of N-nitrosodiethanolamine (NDELA) in cosmetic products were developed. The NDELA fraction was isolated from a cosmetic product by a series of solvent extractions which were designed to concentrate the NDELA and remove ingredients deleterious to the analytical system. The isolated fraction was then analyzed for NDELA using a high pressure liquid chromatograph (HPLC) interfaced with a thermal energy analyzer (TEA). The compound was measured by comparison of detector response with those of known standards. NDELA was verified by gas chromatography-mass spectrometry of the silyl derivative after preliminary cleanup of the sample by gradient elution HPLC on a Partisil 10 PAC column. The limit of detection of NDELA by TEA is 2-3 ng, which corresponds to 20-30 ppb in the cosmetic product. Analysis of an emulsion cream and a hair grooming gel spiked at 3 and 4 ng concentration levels, respectively, yielded recoveries ranging from 71 to 103% (average 88%).

Carcinogens↗

Phenotypes of lung mononuclear phagocytes in HIV seronegative tuberculosis patients: evidence for new recruitment and cell activation.

Mycobacterium tuberculosis preferentially resides in mononuclear phagocytes. The mechanisms by which mononuclear phagocytes keep M. tuberculosis in check or by which the microbe evades control to cause disease remain poorly understood. As an initial effort to delineate these mechanisms, we examined by immunostaining the phenotype of mononuclear phagocytes obtained from lungs of patients with active tuberculosis. From August 1994 to March 1995, consecutive patients who had an abnormal chest X-ray, no demonstrable acid-fast bacilli in sputum specimens and required a diagnostic bronchoalveolar lavage (BAL) were enrolled. Of the 39 patients enrolled, 21 had microbiologically diagnosed tuberculosis. Thirteen of the 21 tuberculosis patients were either HIV seronegative (n = 12) or had no risk factor for HIV and constituted the tuberculosis group. For comparison, M. tuberculosis negative patients who had BAL samples taken during this time (n = 9) or normal healthy volunteers (n = 3) served as control group. Compared to the control group, the tuberculosis group had significantly higher proportion of cells expressing markers of young monocytes (UCHM1) and RFD7, a marker for phagocytic cells, and increased expression of HLA-DR, a marker of cell activation. In addition, tuberculosis group had significantly higher proportion of cells expressing dendritic cell marker (RFD1) and epithelioid cell marker (RFD9). These data suggest that despite recruitment of monocytes probably from the peripheral blood and local cell activation, host defense of the resident lung cells is insufficient to control M. tuberculosis.

Adult↗

Colonoscopy in symptomatic patients with positive family history of colorectal cancer.

BACKGROUND: Most patients with colorectal cancer (CRC) develop clinical signs and symptoms which are not specific for CRC, and usually at a late stage of the disease, resulting in a considerable delay of the diagnosis. In our study we examined patients with bowel symptoms which were at increased risk for developing CRC, because of their family history. METHODS: Over the last 6 years, colonoscopy was performed in 203 patients with colorectal symptoms, who had at least one Ist degree relative with CRC, at the Colorectal Surgery Unit of St George's Hospital. Five hundred ninety two individuals without CRC family history and with either rectal bleeding (n = 479), or with change of bowel habits (n = 113) were used as control group. RESULTS: In the group of patients with family history of CRC 81 colonic lesions were found in 53 patients (53/203, 26%). Patients with family history of CRC were grouped in three categories according to their main symptom. In the subgroup of patients with bleeding (n = 129) there were found 46 colonic lesions in 33 patients. In the subgroup of patients with change of bowel habits (n = 45) we were able to detect 39 colonic lesions. In the group of patients with abdominal pain (n = 29) 4 patients had a metaplastic polyp and one patient had a neoplastic polyp. With regard to the number of 1st degree relatives with CRC, we found that 16/172 (9%) patients with one such relative and 4/31 (13%) of the patients with two relatives were diagnosed with neoplastic polyps. CONCLUSIONS: Total colonoscopy (TC) is an excellent diagnostic procedure for the examination of symptomatic patients with positive family history of colorectal cancer. TC has a diagnostic role detecting the cause of symptoms or excluding the presence of malignancy. Simultaneous resection of the neoplastic and metaplastic polyps, provides an additional, secondary prevention of CRC.

Abdominal Pain↗