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Biomedical subjects

H Goldberg

Publications and source records attributed to H Goldberg.

At least 91 records · Page 5Linked to original sources

Selective toxicity of gossypol against epithelial tumors and its detection by magnetic resonance spectroscopy.

The antitumor toxicity of gossypol was measured in 6 human carcinoma cell lines and compared with its toxicity against human bone marrow stem cells. Marrow cells were more resistant than any of the tumor cell lines, and tumor cell sensitivity depended on the content of intracellular LDH-M. [31P]-Magnetic resonance spectroscopy showed decline in tumor ATP levels occurring within 24 hours of treatment, suggesting that this non-invasive technique may serve as an early biochemical monitor of gossypol toxicity.

Animals↗

Fatal necrotizing fasciitis following suction-assisted lipectomy.

Forty-eight hours following extensive blunt suction lipectomy with 3,000 cc of tissue removed, a 36-year-old woman presented to an emergency room with necrotizing fasciitis of both lower extremities extending over the buttock and to the lower third of the back. Tissue cultures and blood culture grew out a pure culture of beta-hemolytic streptococci. The patient rapidly progressed into a comatose state and, despite extensive debridement and appropriate antibiotic therapy, in addition to hyperbaric oxygen treatments, she died on day 9 of her hospitalization (day 11 following the suction lipectomy). To our knowledge this is the first published mortality reported in the United States following this procedure.

Adipose Tissue↗

Mechanism of Li inhibition of vasopressin-sensitive adenylate cyclase in cultured renal epithelial cells.

We investigated the mechanism for lithium-induced inhibition of vasopressin-stimulated adensoine 3',5'-cyclic monophosphate (cAMP) production in the renal epithelial cell line LLC-PK1. In LLC-PK1 membranes lithium caused direct inhibition of hormone-stimulated adenylate cyclase activity by competing with magnesium. Fifty percent inhibition occurred at 20 mM lithium. The maximum transport activity (Vmax) but not the activation constant (Ka) for activation by vasopressin was altered. Activation by GTP and its nonhydrolyzable analogues was also inhibited by lithium. Furthermore, kinetic studies revealed that the lag phase in the activation of adenylate cyclase by 5'-guanylimi-dotriphosphate [Gpp(NH)p] was prolonged from 1 to 3 min, suggesting an effect of lithium on magnesium-dependent activation of the stimulatory GTP binding protein Gs. The function of the corresponding inhibitory GTP-binding protein Gi, as assessed by GTP inhibition of vasopressin-stimulated adenylate cyclase activity in the presence and absence of pertussis toxin pretreatment, was unaffected. Intact LLC-PK1 cells incubated in 10 mM lithium (approximate urinary concentration in lithium-treated patients) attained an intracellular lithium concentration of 17 mM, which led to a 40% reduction in cAMP formation. Magnesium loading of intact cells with the ionophore A23187 reversed the inhibitory effect of lithium. It is concluded that lithium directly inhibits the activation of vasopressin-sensitive adenylate cyclase in renal epithelia by competing with magnesium for activation of Gs. This direct effect on Gs activation accounts for the inhibitory effect of lithium on cAMP production in the intact cell.

1-Methyl-3-isobutylxanthine↗

Effect of cow's milk on jejunal mucosal macromolecular barrier in suckling guinea pigs.

The assumption that fresh cow's milk may have a direct effect on jejunal mucosal macromolecular permeability was tested in 14-day-old suckling guinea pigs, by in situ luminal perfusion of a proximal jejunal segment with horseradish peroxidase administered either in 0.9% NaCl or in cow's milk. For positive control, a group of guinea pigs previously sensitized to beta-lactoglobulin was similarly perfused with horseradish peroxidase in 0.9% NaCl or in cow's milk at 14 days of age. A segment of the wall of the perfused jejunal loop was processed for peroxidase staining and for examination of the extent and routes of macromolecular absorption by light and electron microscopy. Mucosal exposure to cow's milk was associated with penetration of tracer material across the jejunal epithelium only in the lactoglobulin-sensitized guinea pigs. In guinea pigs with a first-time exposure to cow's milk, no entry of tracer material beyond the brush border surface of the enterocytes was seen. Thus, whereas we could observe absorption of bystander antigens during antigenic challenge of the mucosa in sensitized animals, we found no evidence of a presumptive "permeability factor" in cow's milk that can disrupt the mucosal macromolecular barrier by an acute direct action.

Animals↗

Bordetella pertussis infection: a cause of persistent cough in adults.

An enzyme-linked immunosorbent assay (ELISA) for Bordetella pertussis-specific immunoglobulin (Ig)A antibody in serum was used to demonstrate B. pertussis infection. The upper limit of normal for the assay (mean + 3 SD) was established by testing sera that had been collected from a group of healthy blood donors. All 13 patients with clinical whooping cough from whom B. pertussis was isolated and 25.7% of 218 adults, who were aged 18-81 years, who were referred to a consultant physician for the investigation of a persistent cough, had elevated levels of IgA to B. pertussis. The study confirms the B. pertussis IgA ELISA as a sensitive test for the diagnosis of B. pertussis infections and that these infections cause respiratory illness, in particular, persistent cough in adults.

Adolescent↗

CT body stereotaxis: an aid for CT-guided biopsies.

A new body stereotaxic system used to facilitate CT-guided biopsies is described. By scanning through a triangle placed on the patient's skin, the method defines an entry point for the biopsy. An articulating arm is then used to aim the needle at the entry point and hold the needle at the correct angle. The arm can be angled so that complex approaches from one scan plane to another can be made in order to take biopsies of lesions beneath the diaphragm. Using the system, 23 of 25 lesions were hit on the first needle manipulation; two manipulations were needed for each of the other two lesions. In comparison with previous experience, procedure time was decreased and the numbers of needle manipulations and localization scans were decreased 75% and 90%, respectively.

Biopsy, Needle↗

Superficial temporal-middle cerebral artery anastomosis: effects on vascular, neurologic, and neuropsychological functions.

In 44 patients, we studied the effects of superficial temporal-middle cerebral artery anastomosis on cerebral blood flow (CBF), neurologic examination, and cognitive functions. At 3 months, there was significant improvement in all variables. At 9 months, CBF was no longer significantly greater, but neurologic examination and cognitive functions had further improved. Patients with TIA had significant postoperative decreases in TIA frequency and did not progress to stroke, but had no significant changes in any variable. In stroke patients, we could not separate the effects of surgery from the natural evolution of changes in CBF and examination after stroke. None of the preoperative measurements predicted postoperative clinical improvement.

Adult↗

Improved control of bulky prostate carcinoma with sequential estrogen and radiation therapy.

Patients with bulky prostate cancer have usually been treated by palliative measures because the likelihood of tumor control with definitive irradiation has been low and the development of distant metastases high. The addition of estrogen to irradiation has not been shown to be of value. However, we believe the method of estrogen administration may have been the cause for the apparent lack of benefit. Estrogen had been started either concurrent with irradiation or had been used for palliation and was given for long and unscheduled time periods prior to irradiation. We have used estrogen for two months prior to and concurrent with irradiation. We postulated that in those patients with estrogen responsive cancer, the reduced tumor burden prior to irradiation could enhance tumor control and survival. Between 1975 and 1980, 25 patients with bulky prostate cancer received sequential estrogen and irradiation, 12 patients irradiation alone and six patients irradiation after having become refractory to long-term estrogen use. One patient was lost to follow-up. Eighteen of 25 (72%) treated by sequential estrogen and irradiation, 14/17 (82%) with estrogen responsive cancer and 4/8 (50%) with estrogen resistant cancer had a complete tumor response. Six of 11 (55%) patients treated by irradiation alone and 2/6 (33%) treated by irradiation for estrogen refractory cancer had a complete tumor response. Disease-free survival was observed in 13/25 (52%) treated by sequential estrogen and irradiation, and 8/17 patients (47%) with irradiation. It is also possible the improved survival in the estrogen responsive group was a direct result of improved local control. Persistent local disease can act as a source for distant metastases. Distant metastases was observed in 15% of patients when the primary tumor was controlled and 30% when there was persistent or recurrent local disease. Also, progressive local disease can be an important cause of death. This was most evident in our patients with estrogen refractory cancer. Almost all patients in this group had progressive local disease that caused serious urinary bleeding and urinary infection that were considered the major cause of death. Our results suggest bulky prostate cancer should be aggressively treated when first diagnosed. The value of adjunct estrogen is unproven. Our results with the use of estrogen prior to and concurrent with irradiation is encouraging. Estrogen may shrink the cancer and allow for a more favorable geometry for external irradiation. Tumor control and survival may be thereby improved.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Severe rectal injury following radiation for prostatic cancer.

Between 1970 and 1981, 348 patients underwent definitive irradiation. Of these patients 6 (1.7 per cent) sustained severe rectal injury as manifest by major rectal bleeding, rectal stricture, rectal mucosal slough and rectal ulceration. Severe rectal injury was observed in 0 of 13 patients (0 per cent) treated with 125iodine, 3 of 329 (1 per cent) treated with 6,400 to 6,800 rad external irradiation, 2 of 39 (5 per cent) treated with 7,000 to 7,300 rad external irradiation, and 1 of 7 (14 per cent) treated with 198gold and external irradiation. The impact of radiation dose, radiation therapy technique and surgical trauma was assessed. Rectal injury was managed by supportive measures in 2 patients and by diverting colostomy in 3 with benefit. One patient underwent abdominoperineal resection. A small bowel fistula and an intra-abdominal abscess developed, and the patient died.

Aged↗

Duration of ejection in aortic stenosis: effect of stroke volume and pressure gradient.

The theoretical effect of variable ventricular function on left ventricular ejection time in aortic stenosis was predicted by applying data measured in 52 patients with pure aortic stenosis to equations derived from the relations of Gorlin and Gorlin and Weissler et al. Ejection time and aortic valve area are not, of necessity, linearly related because (Formula: see text) where LVET is left ventricular ejection time, k is a constant, SV is stroke volume, PG is mean aortic pressure gradient and AVA is aortic valve area. When the patients were separated into performance groups on the basis of cardiac index (at 2.8 liters/min per m2), the linear regression relating the measured SV/square root PG with valve area in 18 patients with normal function (SV/square root PG = 11.1 AVA + 2.0, r = 0.969, p less than 0.001) predicted ejection time prolongation with decreasing valve area. In 34 patients with poor function, however, the decrease in SV/square root PG with decreasing valve area was more marked (SV/square root PG = 12.6 AVA + 0.4, r = 0.894, p less than 0.001), predicting a shorter ejection time at any given valve area in this group. As predicted by the effect of valve area on the equation, ejection time becomes most variable at a small aortic valve area. Independent ejection time measurement in these patients validated the predicted effect.

Adult↗

The effect of decentralized education versus increased supply on practice location. Experience with physician assistants and nurse practitioners in California, 1972-1982.

To improve the geographic distribution of physician assistants and nurse practitioners in California, the Primary Care Associate Program established five community-based training sites in outlying areas while continuing to operate its core program within the San Francisco Bay Area. To evaluate this effort, the authors prospectively compared the employment locations of graduates from both groups, achieving a follow-up rate of 95%. Graduates from community sites were twice as likely to locate first practices outside the Bay Area (91% vs. 43%, P less than 0.05) and in towns with less than 10,000 inhabitants (33% vs. 16%, P less than 0.05). Over the decade, the percentage of graduates practicing outside the Bay Area rose from 0 to 9% for trainees both recruited from and entirely trained within the Bay Area versus 76-84 percent for trainees experiencing any element of decentralization. The slopes of these two lines represent the effect of the increasing supply of graduates on practice location away from Stanford (9%); the distance between the lines, the greater effect of decentralization (73%). Given the goal of statewide deployment of a small number of graduates, decentralization appears to have been an effective approach.

Adult↗