Biomedical subjects
J Read
Publications and source records attributed to J Read.
The generation of neurons and oligodendrocytes from a common precursor cell.
We have used a recombinant retrovirus carrying the lacZ gene to study the developmental potential of precursor cells from the embryonic rat cerebral cortex in dissociated cell culture. Virus was used to label a small number of cultured cells genetically so that their fate could be determined. Infected clones were detected with an anti-beta-galactosidase serum, and the labeled cells were identified using monoclonal antibodies. The results revealed that most precursor cells generated a single cell type, the majority being either neurons or oligodendrocytes. However, a proportion of the neuronal clones also included oligodendrocytes. This proportion increased until embryonic day 16 when 18% of the neuronal clones were of this type. This suggests that during neurogenesis in the cerebral cortex there exists a cell with the potential to generate these two quite different neural cell types.
Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guerin or adriamycin. Results of long-term follow-up.
We evaluated 158 cases of patients with superficial bladder cancers (Stages Ta, T1, and Tis). These cases were treated with either intravesical bacillus Calmette-Guerin (BCG) (Tice strain) or Adriamycin (ADR), in a multicenter, nonrandomized study. One hundred thirty-one of these patients were followed up; the results continue to show a higher percentage of initial complete remissions with BCG (68%) than with ADR (57%). With additional therapy, both BCG and ADR achieved complete remission in 83 percent of the patients. When 7 failures with patients taking ADR were switched to BCG and the disease cleared, the rate of complete remission for BCG rose to 85 percent. The recurrence rate per 100 patient-months was only slightly different for BCG (0.9) and ADR (0.8). The percentage of progressions continued to be higher for BCG (8%) than for ADR (5%). Cystectomies were performed in 2.5 percent of the BCG patients. Using the Cox regression model with covariates, we found drug treatment, tumor grade, and sex to be statistically significant in determining failures throughout the protocol. Although both BCG and ADR were effective over the course of the study, BCG is the drug of choice for residual tumor (Stages T1 and Tis).
Analysis of cell lineage in the rat cerebral cortex.
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Read clinical classification.
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Multicenter study of superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin.
We evaluated 155 patients with superficial bladder cancers (Stages Ta, T1, and TIS) and treated them with either intravesical bacillus Calmette-Guérin (Tice strain) (BCG) or doxorubicin hydrochloride (Adriamycin), in a multicenter nonrandomized study. At present 140 of these patients in treatment Groups I and II are being followed up. With additional follow-up, BCG continued to produce a higher percentage of complete remissions (71%) than doxorubicin (54%). The percentage of incomplete remission with BCG (7%) was half that with doxorubicin (14%). Half of the patients whose initial therapy failed had complete remission after additional therapy. However, for patients with recurrence, additional follow-up shows a recurrence rate per 100 patient-months for BCG (1.0) only slightly lower than that for doxorubicin (1.1). The percentage of progressions continued to be higher with BCG (8.5%) than with doxorubicin (5%), but the difference between these results for the two drugs proved slightly less than we reported previously. Of the patients in this study, 2.5 percent (all treated with BCG) required cystectomy. A comparison of the results of our study with those of 13 other studies using BCG to treat bladder cancer indicates that therapy beyond an initial course of 6 weekly treatments increases the percentage of complete response. All of the studies showed that the greatest improvement in percentage of complete response occurred with the second course of treatment. The value of maintenance therapy cannot yet be determined, since few studies have used that protocol. The percentage of patients requiring cystectomy in studies with fewer than 20 treatments was 2.2 times higher than in studies with more than 20 treatments.
A comparison of the high-performance liquid chromatography and RIA measurement of medroxyprogesterone acetate.
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Hydrops fetalis and premature closure of the ductus arteriosus: a review.
The purpose of this report is to describe a case of nonimmune hydrops fetalis that resulted from an unusual congenital heart defect, premature closure of the ductus arteriosus. In this fetus, the ductal closure was not associated with other heart defects such as tetralogy of Fallot or truncus arteriosus, nor was it related to maternal use of nonsteroidal antiinflammatory agents. Despite adequate digitalization of the mother, the fetus died of congestive heart failure at 29 weeks of gestation. Autopsy confirmed stricture of the ductus in association with enlargement of the foramen ovale and marked dilation of the right atrium and main pulmonary artery.
Cotton-wool spots in acquired immunodeficiency syndrome compared with diabetes mellitus, systemic hypertension, and central retinal vein occlusion.
The cotton-wool spot is a common fundus finding in patients with many ocular and systemic diseases. We investigated the characteristics of cotton-wool spots in patients with four major diseases, ie, acquired immunodeficiency syndrome, diabetes mellitus, systemic hypertension, and central retinal vein occlusion, to see if any differences were detected in their number, size, or location. A composite of all the cotton-wool spots for each of these four categories was obtained by computed reconstruction to analyze variations in their distribution and size. The cotton-wool spots had a predilection for the temporal quadrants in the four categories and were smaller in patients with acquired immunodeficiency syndrome than the other groups. Patients with ischemic central retinal vein occlusion had more cotton-wool spots than the other groups. No other definite differences were detected. Cotton-wool spots than the other groups. No other definite differences were detected. Cotton-wool spots seem to be a common pathway following various insults to the retina, most probably of a vaso-occlusive origin.
Superficial bladder cancer treated with intravesical bacillus Calmette-Guérin or adriamycin: follow-up report.
We evaluated 139 patients with superficial bladder cancer (Stages Ta, Tl, and TIS) and treated them with either intravesical bacillus Calmette-Guérin, Tice strain (BCG), or doxorubicin hydrochloride (Adriamycin [ADR]) in a nonrandomized, multicenter study. Our follow-up study comprises 135 of these patients. Of these patients, 78 tumors were completely resected, and 61 were incompletely resected. When a proportional-hazards model (Cox) was applied, there was a statistically significant difference between the recurrence rates for the two drugs. On the basis of recurrence rates per 100 patient-months, both BCG (1.2) and ADR (0.9) worked well with completely resected tumors. However, for incomplete resections, the recurrence rate for BCG (0.9) was less than half that for ADR (1.9). The overall recurrence rates were 1.1 and 1.3 for BCG and ADR, respectively. There have been 42 failures of treatment with either BCG or ADR. We defined failure as any recurrence of tumor; progression of the cancer in stage, grade, tumor number or size; or any residual tumor after 18 treatments (14 months of therapy). As to the failures in patients whom we followed up, and whose treatment was either switched from ADR to BCG or continued on further BCG treatment, 53 per cent have achieved complete remission. Complete remission for BCG and ADR were 76 per cent and 52 per cent, respectively. Of the various factors considered in the study, only tumor grade and treatment drug were statistically significant. The cystectomy rate was 1 per cent for BCG-treated patients and 0 for ADR-treated patients.
Does bacillus Calmette-Guérin immunotherapy accelerate growth and cause metastatic spread of second primary malignancy?
In our study, 29 of 150 patients with bladder cancer also had other associated primary malignancies, 10 of which were manifested after intravesical treatment with bacillus Calmette-Guérin (BCG). Second primary malignancies developed in 5 of these patients within three months of the start of BCG therapy. All 5 showed acceleration of the second primary tumor, and distant metastatic lesions developed in 4. In the other 5 patients nonbladder primary malignancies developed eight months or more after intravesical BCG therapy started, but did not show acceleration or spread. Twenty patients with other primary malignancies that had developed months to years before intravesical therapy did not show acceleration or spread of those tumors. We have seen enough cases of patients who received intravesical BCG at the time of growth and spread of second primary malignancies to warrant concern. Animal and human studies of BCG use for treatment of malignancy indicate that the temporal relationship between the starting point of tumor development and the starting point of BCG treatment is crucial in determining whether BCG will eradicate or exacerbate the tumor. We have therefore instituted a change in our treatment until the question of whether or not BCG causes the appearance and spread of these second malignancies is answered.
A model for in vitro studies of epidermal homeostasis: proliferation and involucrin synthesis by cultured human keratinocytes during recovery after stripping off the suprabasal layers.
In normal epidermis there is a balance between the rate of cell division and the rate of terminal differentiation. This can be perturbed by injuries such as wounding or tape-stripping, but is reestablished during recovery. The aim of the studies described in this report was to assess whether cultures of human keratinocytes could be used as an experimental model for investigating the mechanism by which epidermal homeostasis is established and maintained. The suprabasal layers were stripped from confluent keratinocyte cultures by incubation in low-calcium medium (0.1 mM calcium ions). After return to normal medium (2 mM calcium ions), the basal layer regenerated a stratified culture of approximately the same thickness as controls. The kinetics of proliferation and terminal differentiation were monitored by measuring the total number of cells and proportion of involucrin-positive cells at intervals before, during, and after stripping. During recovery the proportion of cells expressing involucrin, assessed by immunofluorescence microscopy and polyacrylamide gel electrophoresis, rapidly returned to control levels, but the total number of cells per dish rose more slowly and often failed to reach control values. Thus, terminal differentiation was initially stimulated at the expense of proliferation. Our in vitro model of epidermal regeneration should provide a useful complement to intact skin and animal models for analyzing epidermal homeostasis.
Superficial bladder cancer treated by intravesical bacillus Calmette-Guerin or adriamycin: multicenter study interim report.
One hundred sixteen patients with superficial bladder cancers (Stages Ta, T1, and TIS) were evaluated and treated with either intravesical bacillus Calmette-Guerin [Tice strain] (BCG) or doxorubicin hydrochloride (Adriamycin [ADR]), in a multicenter study. One hundred nine of these patients currently have follow-up. Of these, 54 were completely resected and 55 incompletely resected. For complete resections, based on recurrence rates per 100 patient months, both BCG (0.22) and ADR (0.91) worked well, although BCG had a slightly lower recurrence rate. However, for incomplete resections, BCG (0.20) had a markedly lower recurrence rate than ADR (2.52). Eighteen patients failed initial treatment, with either BCG or ADR. All have been placed on long-term therapy schedules. Of the 12 failures who currently have follow-up, 11 (92%) have either partially or completely responded with additional intravesical therapy. No patients in this study have yet required cystectomies.
Dynamic display of the temporomandibular joint meniscus by using "fast-scan" MR imaging.
In order to display temporomandibular joint (TMJ) images as a dynamic or motion study, a protocol was developed to obtain MR images of the TMJ in multiple phases of opening by using the "fast-scanning" capabilities of the GE Signa MR scanner. To facilitate this procedure a prototype device was also developed to passively open the patient's mouth from resting (closed) to fully open in user-defined increments (minimum 1 mm). MR imaging (surface coil) was carried out at each successive station using the GRASS, pulse-sequence data base of the GE Signa system operating at 1.5 T. Image-acquisition parameters were optimized in studies of cadavers and volunteers to obtain the clearest delineation of the TMJ meniscus and to determine any potential tradeoffs between total imaging time per slice (image quality), patient tolerance, and other practical considerations. For viewing, the images were sequentially placed in the video memory of the operating console and displayed in a back-and-forth-closed cine loop or "movie" mode at variable (operator-selectable) speeds. The dynamic sequences in four individuals were compared with static open- and closed-mouth views obtained with routine pulse sequences. Any single image from the dynamic display lacked the high resolution of the routine static images because of technical limitations of the pulse-sequence data base. However, in the movie mode the pertinent joint structures (such as meniscus and condyle) were clearly delineated, as were several of the important muscles of mastication. The anterior motion (translation) of the meniscus during jaw opening is particularly evident and suggests great potential for functional evaluation. These results show the feasibility of dynamic TMJ imaging with MR. The added information of the cine display potentially complements the routine static images and may prove extremely valuable in the assessment of TMJ dysfunction.
The value of lymphoscintigraphy, lymphangiography and computer tomography scanning in the preoperative assessment of lymph nodes involved by pelvic malignant conditions.
In a preoperative study to identify accurately metastases to the lymph nodes within the pelvis and retroperitoneum, the three imaging techniques of pelvic interstitial lymphoscintigraphy, bipedal lymphangiography and computer tomography (CT) scanning were compared in 69 patients with carcinoma of the cervix uteri or rectum. Results were correlated with histologic node examination in all patients and each technique was assessed for sensitivity, specificity and over-all accuracy. Lymphoscintigraphy is too unreliable for routine use in the diagnosis or staging of pelvic malignant conditions. Lymphangiography detects involved lateral pelvic and para-aortic nodes but is unable to visualize the internal iliac or other medial pelvic nodes. CT scanning is only accurate if metastatic nodes are enlarged but may reveal other pathways of spread which will alter the surgical approach.
Postdural puncture headache after continuous spinal anesthesia.
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Simple high-performance liquid chromatographic method for the determination of medroxyprogesterone acetate in human plasma.
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A low cost portable enuresis alarm.
The enuresis alarm described is a portable device designed for 'toilet training' of mentally sub-normal children. It weighs 70 gm with battery, has dimensions of 90 x 60 x 30 mm and conforms to DHSS recommendations. The battery life is over 1000 hours (6 weeks) in continuous use. Total component cost is is pounds 6.20 (in 1978), construction is simple and the circuit may be used as a conventional nocturnal enuresis alarm.