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Biomedical subjects

D Phillips

Publications and source records attributed to D Phillips.

At least 55 records · Page 3Linked to original sources

Failure of gonadotropin therapy secondary to chorionic gonadotropin-induced antibodies.

Seventeen years after first receiving treatment with hCG (at age 8 yr), a man with hypogonadotropic hypogonadism no longer responded to gonadotropin therapy. He had received hCG for 6 months when he was 8 yr old, from age 18-21 yr and from age 21-25 yr, when the resistance developed. Anti-hCG antibodies were found in his serum. Three sequential treatment regimens were tried to obviate the effect of these antibodies. 1) hCG treatment (2000 IU, three times per week) concomitant with weekly plasmapheresis (since the patient's response to an hCG challenge test was improved after a reduction of antibody titer by plasmapheresis) resulted in only a temporary increase in testosterone production. 2) Treatment with human (h) LH (400 IU/week) and hFSH (25 IU/week) was used because of the low cross-reaction of the antibodies with hLH and a response to a hLH-challenge test. This treatment maintained serum testosterone levels within the normal range for long periods, but had to be discontinued when the supply of hLH was exhausted. 3) Pulsatile LHRH administration (25 ng/kg, sc, every 2 h) for 2 months did not induce the release of pituitary gonadotropins. These results indicated that 1) conventional hCG treatment was impaired by antibody-induced changes in the kinetics of hCG after its im administration; 2) hLH was an effective substitute for hCG, and the combined hLH-hFSH administration initiated a moderate amount of spermatogenesis; and 3) the patient differs from most individuals with hypogonadotropin hypogonadism in that he did not have normal responses to repetitive LHRH administration.

Antibodies

Sensitivity of the skin of different mouse strains to the promoting effect of 12-0-tetradecanoyl-phorbol-13-acetate.

The sensitivity of the skin of Swiss DBA/2 and C57B1/6 mice was compared in two-stage carcinogenicity experiments. Groups of 30 mice were treated once with 7,12-dimethylbenz(a)anthracene (DMBA) (50 micrograms/mouse) which was applied to the shaved dorsal skin as initiator and, starting one week later, 12-0-tetradecanoyl-phorbol-13-acetate (TPA) was applied thrice-weekly at doses of either 0.04, 0.16 or 0.64 micrograms/mouse to the areas of initiated skin. Other groups of mice were similarly treated with TPA (0.64 micrograms) alone. The times at which papillomas and carcinomas first appeared were recorded. Overall the results show, in terms of the numbers of animals with tumours, the total numbers of tumours produced and the numbers of malignant tumours formed all in dose-response relationship, that the Swiss mice were the most sensitive and the B57B1/6 mice the least sensitive to the tumour-promoting effects of TPA with the DBA/2 mice occupying and intermediate position. This relationship also held in the control groups that were treated with TPA alone.

9,10-Dimethyl-1,2-benzanthracene

Metabolic and thermoregulatory consequences of social behaviors between Microtus townsendii.

1. Townsend voles responded to each other by raising their core temperatures. 2. Increments of temperature increases that accompanied hostile reactions between voles, were proportional to the intensity of the behavioral displays. 3. Amicable behaviors (huddling) were also associated with higher body temperatures that were proportional to group size. 4. Huddling voles conserved metabolic energy expenditure by reducing their metabolic rates and thermal conductances. 5. Such conservation required 1 or more days of amicable behavior to develop, and to be reversed. 6. The degree of metabolic rate reduction that accompanied amicable huddling behavior and the associated reduction of thermal conductance was independent of group size.

Animals

Cellular and protein changes in bronchial lavage fluid after late asthmatic reaction in patients with red cedar asthma.

To investigate the sequence of cellular and protein changes after a late asthmatic reaction (LAR), bronchial lavage was carried out in 44 patients with red cedar asthma at different time intervals after bronchial challenge with plicatic acid. The results were compared to five patients with red cedar asthma who became asymptomatic after removal from exposure to red cedar for more than 2 months and 31 healthy subjects without asthma. The LAR was found to be associated with an increase in eosinophils in the lavage fluid, an increase in sloughing of bronchial epithelial cells, and an increase in degenerated cells consisting mainly of degenerated epithelial cells and alveolar macrophages. There was an increase in vascular permeability as reflected by an increase in albumin in the lavage fluid. Although there was a slight but significant increase in neutrophils 48 hours after bronchial challenge, neutrophil infiltration was not a prominent feature earlier. The potential role of loss of epithelial cells to account for an increase in nonspecific bronchial hyperresponsiveness after an LAR was discussed.

Adult

Long-term immunization against the beta-subunit of ovine luteinizing hormone (oLH beta) has no adverse effects on pituitary function in rhesus monkeys.

One postulated safety hazard of contraceptive methods based on immunization against gonadotropic hormones is the possibility that circulating antibodies which crossreact with pituitary hormones may impair pituitary function through the deposition of immunoglobulin and/or complement suggesting immune complexes. In order to evaluate this possibility in rhesus monkeys actively immunized against the beta-subunit of ovine luteinizing hormone (oLH beta), we used three approaches to study the effects of long-term immunization on pituitary function: a) evaluation of pituitary responsiveness to challenge with a GnRH-agonist; b) examination of pituitary histology and immunostaining with gonadotropin antisera; and c) examination of pituitary cells for deposition of immune complexes. Our results indicate that circulating anti-oLH beta antibodies did not result in significant impairment of pituitary function in rhesus monkeys.

Animals

Immunohistochemistry of the blood group A,B,H isoantigens and Oxford Ca antigen as prognostic markers for stage IB squamous cell carcinoma of the cervix.

Currently, there is lack of a histologic classification of squamous cell carcinoma of the cervix that correlates significantly with patient survival. This study investigated the survival predictive value of two immunohistochemical markers, the blood group A,B,H isoantigens and the Oxford Ca antigen, on conventional histologic sections of tumor tissues from 85 surgically treated patients with Stage IB squamous cell cervical cancer. The results indicated that the two antigens are two distinct markers, neither of which correlates with tumor grade. The expression of the A,B,H isoantigens is significantly related to patient survival after adjustment for the depth of stromal invasion of the tumor, whereas the Oxford Ca antigen has no survival predictive value.

ABO Blood-Group System

Malignant transformation of NIH-3T3 and CV-1 cells by a helical mycoplasma, Spiroplasma mirum, strain SMCA.

A helical mycoplasma, Spiroplasma mirum strain SMCA, produced malignant transformation in mouse NIH 3T3 cells and monkey kidney CV-1 cells. The transformed cells exhibited morphological changes consistent with the transformed phenotype, grew in soft agar and produced tumors in athymic and BALB/c mice. Transmission electron microscopy revealed structures morphologically similar to mycoplasmas present in the cytoplasm of transformed but not untransformed 3T3 cells. The time of inoculation of S. mirum SMCA to 3T3 cells and the passage level of 3T3 cells affected transformation.

Animals

Treatment of acute mesenteric ischemia by percutaneous transluminal angioplasty.

A 79-yr-old man with previously documented atherosclerotic vascular disease presented with acute abdominal pain, signs of peritoneal irritation, and guaiac-positive stool. A mesenteric arteriogram showed high-grade stenosis of the superior mesenteric artery with a pressure gradient of 70 mmHg and complete occlusion of the inferior mesenteric artery. Percutaneous transluminal angioplasty of the superior mesenteric artery was performed with immediate reduction of the pressure gradient, increase in vessel caliber, and relief of abdominal pain. The patient went on to complete recovery and remains pain-free 6 mo after discharge from the hospital. To our knowledge, this is the first report of percutaneous transluminal angioplasty used to treat acute mesenteric ischemia.

Acute Disease

Phalangeal osteochondroma: an unusual cause of swan-neck deformity.

A 4-year-old child with a proximal phalangeal osteochondroma of the index finger presented with a rigid swan-neck deformity. The dorsal apparatus overlying the tumor was stretched, causing increased tension on the central slip and thus hypertension of the proximal interphalangeal joint. Excision of the tumor resulted in complete restoration of digital motion.

Bone Neoplasms

Cell uptake, distribution and response to aluminium chloro sulphonated phthalocyanine, a potential anti-tumour photosensitizer.

The uptake, retention and effects of aluminium chloro sulphonated phthalocyanine (AlSPc) were measured in two cell lines, UV-2237 a murine fibrosarcoma and the non-tumorigenic NIH/3T3 fibroblast line. The behaviour of cells treated with AlSPc was compared with that of those treated with haematoporphyrin derivative (HpD), a photosensitizer often used in photodynamic therapy (PDT) of cancer. AlSPc absorbs light strongly in the red region, is taken up by cells in a dose dependent fashion and is retained in vitro over a period of days (5 days after exposure greater than 40% remains cell-associated versus less than 25% of HpD). Additionally AlSPc was less cytotoxic to cells, maintained in darkness or exposed to room light, compared to HpD (100% viability versus 0% viability 3 days after 60 min exposure to room light). However red light (approximately 600-700 nm) caused greater toxicity in AlSPc-treated cells (100%) than in similarly exposed HpD-treated cells (less than 60%). No significant differences were detected between the responses of the fibrosarcoma and the fibroblast cell lines. These characteristics of AlSPc suggest that it may prove to be a useful photosensitizer for PDT of cancer and this possibility is discussed.

Animals

Controlled trial of thyrotropin releasing hormone in amyotrophic lateral sclerosis.

A double-blind controlled trial of thyrotropin releasing hormone (TRH) 150 mg IM daily in 30 patients with amyotrophic lateral sclerosis is reported. The drug/placebo was administered for 2 months, followed by a 2-month "wash-out". Evaluation of strength, functional ability, and respiratory functions was performed. A temporary increase in the strength of some muscles was detected following the administration of TRH, but no change in functional performance was noted. Neither the patients nor the investigators believed the effects were of any marked clinical significance. The course of the illness was not altered.

Adult

Vinblastine plus cisplatin in advanced non-small cell lung cancer: lack of advantage for vinblastine infusion schedule.

We have evaluated 31 patients with advanced non-small cell lung cancer treated by short-term 5-day vinblastine infusion combined with bolus cisplatin. Nine of 31 patients (29%) had partial and complete responses. Although five of nine (55%) of the responders were alive at greater than or equal to 1 year, three of the 31 patients experienced drug-related mortality. Our experience, as well as a review of previously reported trials in the literature, suggests that the infusion schedule of vinblastine offers no advantage over the bolus schedule.

Adenocarcinoma

5-Fluorouracil and methotrexate administered simultaneously as a continuous infusion. A phase I study.

Infusion delivery systems have been evaluated for administration of many individual chemotherapeutic agents including 5-fluorouracil (5-FU) and methotrexate (MTX). This study combined the two drugs as an admixture, and in a Phase I trial design established a useful dose schedule for each of the component drugs. 5-FU at a fixed dose rate of 300 mg/M2/day was delivered with methotrexate (MTX) at four different dose rates (0.75, 1.0, 1.5, or 2.0 mg/M2/day, respectively). The drug solution was delivered via a subclavian venous access with a portable infusion pump in an ambulatory setting. Twenty-nine patients received a total of 38 courses of the two-drug infusion: 21 courses were delivered with the two agents admixed constantly throughout treatment (Schedule A) and 17 were administered the treatment with 5-FU delivered continuously and MTX added to the 5-FU for alternate 14-day cycles (Schedule B). For the former schedule, dose-rate-limiting toxicity was related to MTX and included stomatitis developing at days 8 to 14 (median, day 8) with the higher dose rates (1.5-2.0 mg/M2/day) and thrombocytopenia developing at days 11 to 56 (median, day 14) at the lowest dose rates (1.0 mg/M2/day). For Schedule B, dose-rate-limiting toxicity was similarly due to the MTX with thrombocytopenia and/or chemical hepatitis developing in six of seven courses of MTX at 1.0 mg/M2/day and in five of ten courses delivered at 0.75 mg/M2/day. On Schedule B the MTX-associated toxicities were reversed when the MTX administration was interrupted and in the face of continued 5-FU infusion. A reasonable dose rate and schedule for continuous infusion of 5-FU combined with MTX is: 5-FU 300 mg/M2/day X 28 days and MTX 0.75 mg/M2/day for days 1 to 14, with cycles administered consecutively each 28 days.

Adult