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Biomedical subjects

B L Johnson

Publications and source records attributed to B L Johnson.

At least 19 recordsLinked to original sources

Serum and blister fluid pharmacokinetics and bactericidal activities of ampicillin-sulbactam, cefotetan, cefoxitin, ceftizoxime, and ticarcillin-clavulanate.

Ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, and ceftizoxime are promoted for the treatment of mixed aerobic-anaerobic bacterial infections. Their activities have been compared in vitro but not in vivo. In order to assess the in vivo activities of these agents in serum and interstitial fluid, we administered single, intravenous doses of these antimicrobial agents to healthy subjects. Concentrations of the antimicrobial agents in serum and suction-induced blister fluid and bactericidal activity were measured by high-pressure liquid chromatography and the standard methodology of the National Committee for Clinical Laboratory Standards, respectively. The organisms used for bactericidal activity tests were one isolate each of Staphylococcus aureus, Klebsiella pneumoniae, and Bacteroides fragilis. Pharmacokinetic parameters in serum and blister fluid were similar to those derived in other investigations. Of note were the high and prolonged concentrations of ticarcillin and cefotetan in blister fluid, despite high-level serum protein binding. The bactericidal activities in serum and blister fluid reflected the relative in vitro activities and kinetic dispositions of the various antimicrobial agents except for the bactericidal activity of cefotetan, which was substantially lower in blister fluid than serum, despite a blister fluid:serum area under the concentration-time curve ratio of 1.5. Similarly, the activity of ticarcillin-clavulanate in blister fluid was also substantially less than would have been predicted by the blister fluid:serum ratio of the area under the concentration-time curve of 1.1, possibly because of the low concentrations of clavulanate in blister fluid. The rankings of the in vivo bactericidal activities of the five drugs were as follows: for S. aureus, ampicillin-sulbactam > ticarcillin-clavulanate > ceftizoxime > cefoxitin > cefotetan; for K. pneumoniae, ceftizoxime > cefotetan > ampicillin-sulbactam = ticarcillin-clavulanate > cefoxitin; and for B.fragilis, ticarcillin-clavulanate > cefotetan > ceftizoxime > ampicillin-sulbactam = cefoxitin.

Adult

Signet cell melanocytic lesions.

Malignant melanoma can produce diagnostic problems for the histopathologist because of its protean histologic patterns. The recently recognized signet cell pattern can be particularly confusing and must be distinguished from adenocarcinoma, tumors of vascular endothelium or adipose tissue, lymphoma, and epithelioid smooth muscle lesions. We report four new cases of signet cell melanoma and illustrate this pattern in primary as well as metastatic sites. In addition, we document the signet cell pattern in benign nevi for the first time, expanding the concept of this pattern to melanocytic cells in general. The differential diagnosis of signet cell melanoma and its mimics is discussed and the utility of immunohistochemical stains in this diagnosis is stressed.

Adult

Spindle cell lipoma of the orbit.

A 42-year-old woman had an orbital mass lesion removed surgically that proved histologically to be a spindle cell lipoma. To our knowledge, this is the first reported case of a spindle cell lipoma arising in the orbit. This specific type of lipoma occurs chiefly in male patients and is believed to affect the shoulder and posterior neck regions almost exclusively. Spindle cell lipomas, while having unusual features histologically, are benign and should not be mistaken for liposarcomas or other spindle cell soft-tissue tumors.

Adult

Ocular findings in Kenny's syndrome.

In 1966, Kenny described two patients with an unusual congenital syndrome including dwarfism, thickened long bone cortex, transient hypocalcemia, and normal intelligence. These and other patients previously were incorrectly described as "myopic". Ocular findings in four subjects ranged from uncomplicated nanophthalmos with hyperopia to extreme pseudopapilledema, vascular tortuosity, and mucular crowding. Postmortem findings from one patient showed calcium deposits demonstrable only by special histochemical stains that were distributed uniquely in the cornea. This distribution differed greatly from the pattern seen in band keratopathy. Retinal calcification was also an unusual feature. Because one patient exhibited a pseudodoubling of the optic papilla, the literature was reviewed. We conclude that no convincing case of true doubling of the optic nerve has been described. Ophthalmologists should be alert for undiagnosed electrolyte abnormalities, especially hypocalcemia, in patients with Kenney's syndrome.

Adolescent

Fine-needle aspiration biopsy. Its use in orbital tumors.

Fifteen orbital tumors have been evaluated with the fine-needle aspiration biopsy (FNAB) technique. The best indication for FNAB is supposed malignant orbital disease. The technique has not been helpful in tumors or inflammatory disease with a high fibrous content. Lesions that are suspected of being pseudotumors are not recommended for FNAB since, even in histologic sections, they are notoriously difficult to distinguish from well-differentiated lymphocytic malignant lymphoma. Benign encapsulated tumors should not be subjected to FNAB.

Adult

Radiation treatment of orbital lymphoid hyperplasia.

Ten patients with biopsy-proved lymphoid hyperplasia (pseudotumor) of the orbit were treated with radiation therapy individed sose ranging from 2,500 to 3,000 rads. Five of the ten patients had prior treatment with corticosteroids in high dosages with only partial or no response. All ten patients had clinical resolution of the lymphoid hyperplasia orbital mass within three weeks following radiation therapy. A follow-up period of six months to five years has demonstrated no recurrences. There were no discernible complications from the radiation therapy. We believe that radiation therapy should be considered as a primary treatment of benign lymphoid hyperplasia of the orbit.

Aged

Ocular dermoid.

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Adult

Hexamethylmelamine in alkylating agent-resistant ovarian carcinoma.

Twenty-one patients with advanced ovarian cancer proven resistant to standard alkylating chemotherapy were evaluated in a prospective study of Hexamethylmelamine. All but three patients received 8 mg/kg daily with dose modifications appropriate to the degree of toxicity; the latter three patients were treated on an intermittent 14 day course of 8 mg/kg daily. Six patients (28%) experienced an objective response with a median duration of 2.5 months (range 1--5 months). The toxic effects requiring dose modification were gastrointestinal in 57%, hematologic in 62%, and neurologic in 28.5%. An average of 60.5% of the total projected dose was tolerated for a median of 44 days (range 7--113). Twelve patients (57%) experienced severe toxicity requiring discontinuation of therapy. It is apparent from this study that Hexamethylmelamine is an active agent in ovarian cancer and is not invariably cross-resistant to conventional alkylating agent therapy. These two characteristics make it an attractive agent for use in combination. Its toxicity in previously treated patients in the schedules used here, however, is substantial.

Adenocarcinoma

A simple technique for removal of recurring granular dystrophy in corneal grafts.

A 63-year-old man and his 24-year-old son developed recurrences of granular dystrophy in their three corneal grafts within three years after surgery. We regrafted one of the son's corneas. Histologic examination of the corneal button removed during surgery showed an avascular connective tissue layer with the histochemical characteristics of granular dystrophy interposed between the epithelium and Bowman's layer. In the remaining two corneal grafts, we fixed the globe with corneal forceps and removed the opaque dystrophic layer by separating it from the cornea with a spatula. Postoperatively, all three corneal grafts were once more transparent.

Adolescent

An electrodiagnostic study of the neurotoxicity of methyl n-amyl ketone.

The neurotoxicity of methyl n-amyl ketone was investigated in a chronic inhalation study lasting 9 months. Rats and monkeys were exposed 6 hrs/day, 5 days/week, to mean MAK levels of 0, 131, and 1025 ppm. Electrodiagnostic measures of nervous system function revealed no neurotoxic impairment at either MAK exposure. Body weights were similarly unaffected. Gross and histopathology also indicated no adverse effects of MAK. It was concluded that MAK does not possess neurotoxic properties similar to those possessed by methyl n-butyl ketone.

Action Potentials

Posterior polymorphous dystrophy: a light and electron microscopic study.

Microscopic study of a keratoplasty specimen in a case of posterior polymorphous dystrophy demonstrated via serial sections a multilaminar Descemet's membrane with focal fusiform nodular protrusions of connective tissue. The latter are thought to represent the polymorphous lesions of the posterior limiting layers of the cornea seen clinically. Ultrastructurally, fibroflast-like cells lined the posterior surface of the cornea. It is postulated that those reported cases of PPD in which epithelial-like transformation of the endothelial layer has been described may represent more advanced cases, in which corneal oedema is likely to be a prominant feature clinically. An evolving process of metaplasia rather than a static one might explain the variety of altered endothelial cells, fibroblasts, and epithelial cells which have been reported on the posterior cornea in the few PPD keratoplasty specimens studied to date.

Adolescent

Initial clinical trials of maytansine, an antitumor plant alkaloid.

We have conducted a phase I clinical trial of maytansine, a plant alkaloid with potent tubulin-binding activity. For evaluation of toxicity, the schedule of drug administration consisted of a single iv infusion given every 3 weeks. Dose-limiting toxicity was observed at 2 mg/m2, and was manifested as profound weakness, diarrhea, nausea, and vomiting. Symptoms persisted for 3--14 days after drug administration. No consistent myelosuppression occurred at any dose level. Responses were observed in two patients (one each with non-Hodgkin's lymphoma and ovarian cancer) who were treated on the every-3-week schedule, as well as in two patients with acute lymphocytic leukemia treated with single weekly doses. Three of the four responding patients had received extensive prior treatment with vincristine, and two were clearly resistant to vincristine.

Adolescent

Prognostic factors for advanced diffuse histiocytic lymphoma following treatment with combination chemotherapy.

Combination chemotherapy can dramatically improve the survival of those patients with advanced diffuse histiocytic lymphoma who enter complete remission. The age, sex, stage, constitutional symptoms, sites of disease and tumor mass of 56 consecutive patients with advanced diffuse histiocytic lymphoma were analyzed as prognostic factors. Twenty-four patients received cytoxan, vincristine, procarbazine and prednisone (C-MOPP) and 32 patients received bleomycin, adriamycin, cytoxan, vincristine and prednisone (BACOP). In 26 of 56 (46 per cent) a complete remission was achieved, in 21 of 56 (38 per cent) a partial remission and in nine of 56 (16 per cent) no response. Median survival with a complete remission was not reached at three years with 82 per cent still alive, but was significantly greater than with a partial remission (7.6 months median) or no response (3.2 months median). Survival of those with a partial remission and no response did not differ statistically. Stage IV disease, bone marrow involvement, gastrointestinal involvement and a tumor mass greater than 10 cm in diameter in a single location were all poor prognostic factors. No other analyzed factor significantly affected survival in this study. Complete response rates and survival curves for patients treated with C-MOPP were similar to those treated with BACOP.

Adult