Osteomyelitis and the natural history of disease. A model for approaching podiatric disorders.
Explore the source record for details and available documents.
Foot Diseases↗
Biomedical subjects
L Levy
Publications and source records attributed to L Levy.
Role of the popliteal lymph node in infection with Mycobacterium marinum of the hind footpad of the mouse, and source of the cells that characterize the process.
We examined the possibility that the popliteal lymph node serves as the source of the lymphocytes that, together with macrophages, characterize the lesion produced by infection with Mycobacterium marinum in the hind footpad of the mouse. Naïve mice were partially protected against challenge with M. marinum in the hind footpad by intravenous infusion of lymphocytes harvested from the popliteal nodes of donor mice infected with M. marinum 7 days earlier. Lymphocytes harvested from the popliteal nodes of infected donors, labelled in vitro with 3H-uridine, and infused intravenously into naïve mice that were immediately challenged in the hind footpads with M. marinum, localized in the popliteal nodes of the recipient mice but not in the footpad lesions. Lymphocytes harvested from the spleens of naïve donors and labelled in vitro appeared to home to the popliteal node draining the M. marinum-infected footpad. Thus, the primary role of the popliteal lymph node appeared to be passive trapping of the lymphocytes brought to it by the circulation or afferent lymphatics. We then tried to locate the sources of both lymphocytes and macrophages that characterize the lesion. Temporary occlusion of the abdominal aorta prevented labelling by intravenously infused 3H-thymidine (3H-TdR) of the mononuclear cells of both footpad lesion and popliteal node. Temporary occlusion of the left common iliac artery during 3H-TdR infusion prevented immediate labelling on the ipsilateral side. After 24 and 48 h, however, small numbers of labelled lymphocytes were found in the left hind footpad lesion. Amputation of the right leg at the hip joint, but not right popliteal lymphadenectomy, performed immediately after re-establishment of patency of the left common iliac artery, prevented the late influx of labelled lymphocytes into the lesion of the left hind footpad. Thus, the chief source of both the lymphocytes and the macrophages of the footpad lesion appeared to be the lesion itself.
Animals↗
Effects of pulse cyclophosphamide on NZB/W disease.
Induced IgM anti-ss-DNA antibodies in NZB/W female mice did not alter the time of onset nor the course of nephritis. Monthly pulse doses of cyclophosphamide suppressed the mortality of these mice, and also prevented a switch of anti-ss-DNA from IgM to IgG class. The production of IgM anti-SRBC was markedly reduced in old NZB/W mice, but IgG anti-SRBC was only moderately reduced and this hyporesponsiveness towards SRBC could be reversed by CPA treatment. These observations are discussed in relation to cyclophosphamide as an effective therapeutic agent for the murine lupus syndrome.
Age Factors↗
Activity of four clofazimine analogues against Mycobacterium leprae.
Explore the source record for details and available documents.
Animals↗
Response in the hindfoot pad and popliteal lymph node of C57BL mice to infection with Mycobacterium marinum.
C57BL mice inoculated in the hindfoot pads with 5 X 10(3) viable Mycobacterium marinum developed a localized disease process, characterized by swelling of the foot and increases in the number of acid-fast bacilli and colony forming units recovered. These changes became maximal 10 to 14 days after inoculation and then decreased in intensity. An acute inflammatory response appeared in the hindfoot pad during the first 24 h and increased in intensity during the next few days. By seven days after inoculation, the polymorphonuclear leukocytes had been largely replaced by lymphocytes and macrophages which led, during the next two weeks, to the extensive formation of granulomas. Epithelioid granulomas developed after at least 90% of the organisms had been killed. Simultaneously the popliteal lymph node increased greatly in size due to hyperplasia of the paracortical area, which contained a large number of pyroninophilic cells, and packing of sinusoids with small lymphocytes. Well-formed epithelioid granulomas containing acid-fast bacilli developed in the popliteal node. A small number of viable bacilli were found in both the hindfoot pad and the popliteal node 18 months after inoculation; this was accompanied by solid resistance to secondary challenge.
Animals↗
The effect of alpha-adrenergic innervation on caudate blood flow.
A thermal diffusion probe, with cannulas for intracerebral microinfusion of drugs and an electrode to monitor electroencephalographic (EEG) activity, was used to examine the local effect of vasoactive amines in a 4 to 5 mm sphere of caudate nucleus in cats. The results demonstrated that it is possible to alter local cerebral blood flow (CBF) without causing any change in systemic blood pressure or heart rate, or in CBF and the EEG in the opposite caudate. One-microliter intracerebral injections, containing varying amounts of phenylephrine, increased local CBF in proportion to dose. The effect was blocked by intracerebral infusion of phentolamine. However, local alpha-adrenergic blockade did not inhibit vascular responses to blood pressure elevation or to metabolic influences on local blood flow.
Adrenergic Fibers↗
Response in distant lymph nodes of mice to infection in the hind footpad with Mycobacterium marinum.
In an attempt to demonstrate the importance of the popliteal lymph node in limiting the progress of infection with Mycobacterium marinum in the hind footpads of C57BL mice, such infections were studied in mice subjected to popliteal or popliteal and inguinal adenectomies. In the absence of the popliteal node, the footpad infection was only slightly enhanced compared with infections of sham-operated control mice; the inguinal node was found to be greatly enlarged and appeared to have substituted for the absent popliteal node. In the absence of both popliteal and inguinal nodes, the disease process in the footpads was again only slightly enhanced, and the axillary node appeared to have enlarged greatly and to have functionally replaced the missing, more proximate nodes. In additional experiments, mice subjected to adenectomy only on one side and injected in that hind footpad with phytohemagglutinin or India ink demonstrated hypertrophy or deposition of carbon particles in the more distant node only on the side of the injection. Thus, there appear to be rather direct functional connections among popliteal, inguinal, and axillary nodes that do not depend on blood circulation.
Animals↗
Viability of Mycobacterium leprae after multiplication in mice.
To measure the rate at which Mycobacterium leprae are killed in the course of the mouse footpad infection after the maximum of multiplication has been achieved, M. leprae were harvested shortly before and at intervals after multiplication had reached the level of 10(6) organisms per footpad, serially diluted, and inoculated into the footpads of passage mice. Beginning 1 year later, foot-by-foot harvests of M. leprae were performed from passage mice, and the proportion of viable organisms in the passage inocula was calculated by means of a most-probable-number calculation. In addition, the proportion of solidly staining M. leprae was measured in the passage inocula. The proportion of viable M. leprae in the passage inocula was found to decrease with the time after multiplication to 10(6) organisms per footpad of donor mice; the half-time of loss of viable M. leprae was 25 days. The proportion of solidly staining organisms appeared to be directly related to the proportion of viable organisms, as measured by mouse passage, and inversely proportional to the time after multiplication to 10(6) organisms per footpad.
Animals↗
Combined rifampin and dapsone chemotherapy of Mycobacterium leprae infection of the neonatally thymectomized Lewis rat.
Neonatally thymectomized Lewis rats (NTLR) were shown to be highly susceptible to infection with Mycobacterium leprae. We have used them in chemotherapeutic studies as models of human lepromatous leprosy. NTLR chronically infected with M. leprae were treated with various regimens combining a background of the minimal effective dose (MED) of dapsone (4,4'-diaminodiphenylsulfone, DDS) or 100 times this dose in the diet with one to ten doses of rifampin (RMP) of 10 mg/kg. To test for persisting viable M. leprae passage of 5 X 19(3) organisms was made to intact mice, and 10(5) to 10(7) acid-fast bacilli were passaged to NTLR. The only regimen that appeared to be completely effective in eliminating infectivity for intact mice was ten doses of RMP given on the background of the MED of DDS. No viable organisms were detected in any passage mice, but multiplication of M. leprae was detected in 12 of 16 passage NTLR, representing three of the four groups in which passage was made. In no instance did we fail to detect organisms in passage of NTLR when we detected them in passage mice, and multiplication was demonstrated in passage NTLR in 14 instances in which M. leprae failed to multiply in passage mice. Because of its high degree of immunosuppression, the NTLR was able to detect a small population of viable M. leprae in inocula containing up to 5000 times the number of organisms that can be inoculated into intact mice. The NTLR appears to provide a model for the study of microbial persistence in leprosy.
Animals↗
Survival of BALB/c mice after intraperitoneal infection with Mycobacterium lepraemurium.
In an attempt to develop a single, quantitative method of studying the disease that follows infection of susceptible mice with Mycobacterium lepraemurium, survival of BALB/c mice was measured as a function of time following i.p. inoculation with the organisms. Survival was found to be inversely related to the challenge dose of M. lepraemurium and unrelated to the organ-source of the organisms; survival was prolonged by treatment with isoniazid. Mice infected with M. lepraemurium were protected against i.v. challenge with M. marinum administered early in the disease, whereas they demonstrated enhanced susceptibility to the same challenge administered later. Conversely, prior M. marinum infection of mice in the hindfoot pad conferred protection against subsequent challenge with M. lepraemurium.
Animals↗
Survival of BALB/c mice after intravenous infection with Mycobacterium marinum.
In a search for a simple technique by which to study the disease of mice that follows infection with Mycobacterium marinum, survival of BALB/c mice after i.v. inoculation of M. marinum was measured. Length of survival was inversely proportional to the number of viable organisms in the inoculum, and was greater in weanling than in yearling mice. Prior infection with M. marinum in a hindfoot pad at least two weeks before i.v. challenge with the same organism conferred protection against the challenge.
Animals↗
Cadmium and the reticuloendothelial system (RES). A specific defect in blood clearance of soluble aggregates of IgG by the liver in mice given cadmium.
The ability of the reticuloendothelial system (RES) to bind and catabolize soluble stable heat aggregates of 125I-IgG (A-IgG) was studied in mice given oral cadmium. Cadmium caused a delay in the circulation clearance of A-IgG in intact animals. The defect was due to impaired liver uptake of A-IgG and correlated with increased liver cadmium. Subsequent catabolism of bound A-IgG by liver slices was not affected. The defect was specific in that clearance of aggregated human serum albumin and colloidal carbon was normal in cadmium mice; this suggests that cadmium may affect either Fc or complement receptors of Kupffer cells in liver.
Animals↗
Protection of mice by intraperitoneal vaccination against challenge in the foot pad with Mycobacterium marinum.
In a study of local infection of mice with Mycobacterium marinum, heat-killed M. marinum suspended either in Hanks' balanced salt solution or in Freund's incomplete adjuvant was administered i.p. to BALB/c mice. The mice were challenged in the hind foot pad 3, 7, or 14 days thereafter with 5 x 10(3) viable M. marinum. At every time interval, killed M. marinum in the saline medium conferred modest protection against the challenge infection, whereas the antigen suspended in adjuvant conferred protection only when the challenge was administered 14 days after vaccination. Freund's incomplete adjuvant appeared to enhance the infection and to minimize the immune response to the antigen.
Animals↗
A novel fluorinated derivative of diethylstilbestrol.
The synthesis of the diethylstilbestrol (DES) derivative with fluorine atoms present in the positions ortho to the hydroxyl in each ring is described. In vitro studies in a system containing horse radish peroxidase/H2O2 demonstrate extensive oxidation of tetrafluorodiethylstilbestrol to the corresponding dienestrol derivative. Tetrafluorodiethylstilbestrol and DES had comparable in vivo uterotropic activities at a dose of 100 microgram/kg. Competitive binding experiments demonstrated 20-25 fold reduced interaction with the mouse uterine estrogen receptor. This compound may be useful as an experimental estrogen in distinguishing between the biological and toxic effects of DES.
Animals↗
Dynamic renal scan in the non-visualizing kidney.
Thirty-one patients with 35 non-visualizing kidneys on excretory urography were studied with 99mtechnetium-diethylenetriaminepentaacetic acid scintiscanning. In 11 cases good renal blood flow and concentration were demonstrated on nucleide scanning. All patients had significant parenchyma and recoverable renal function after appropriate surgical management. In 20 cases there was little or no blood flow on the scan. These patients either had a congenitally absent kidney or severely destroyed parenchyma. The 99mtechnetium-diethylenetriaminepentaacetic acid dynamic renal scan is a sensitive method for predicting renal salvageability of a kidney that fails to visualize on excretory urography.
Adolescent↗
Liaison podiatry: a vehicle for developing closer collaboration with medicine.
Explore the source record for details and available documents.
Interprofessional Relations↗
The metabolism of nucleic acids in mice.
The metabolism of three forms of nucleic acid, native-DNA (N-DNA), single strand DNA (SS-DNA), and polyinosinic-polycytidylic acid (poly I : C), was investigated in vivo in randomly bred Swiss-Webster mice. Clearance of these substances from the circulation and tissue localization were determined at selected time intervals following the intravenous injection of 125I-labelled compounds. N- and ss-DNA were removed from the circulation more rapidly than was poly I : C. All three materials localized principally in reticuloendothelial-rich organs, i.e. liver and spleen. N-DNA was degraded by the liver more slowly than was poly I : C or ss-DNA. At 4 h following injection, the liver contained 26%, 13%, and 10% of the injected doses, respectively. Three days after injection, 4.5% of the N-DNA persisted in the liver, as compared to only 0.6% of the poly I : C, and 0.2% of the ss-DNA. The possiblity that these differences in metabolism of N-DNA, poly I: C, and ss-DNA may be related to their differing immunogenic potentials in experimental systems is discussed.
Animals↗
Effect of pulse dose cyclophosphamide on the anamnestic immune response in NZB/W mice.
Mice exhibiting a spontaneous SLE-like lethal autoimmunity (female NZB/W hybrids) were given monthly doses of cyclophosphamide (CPA) 240 mg/kg p.o. starting at four months of age. Antibodies to DNA and sheep red blood cells (SRBC) were measured as well as general well being of the mice. The CPA-treated group demonstrated a marked increased in survival compared to the untreated controls with reduction of anti-DNA antibody levels but only a slight inhibition of the anamnestic response to SRBC immunization.
Animals↗