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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 109 records · Page 6Linked to original sources
PubMed1990

Pharmacological activities of delta-aminolaevulinic acid, protoporphyrin IX and haemin in isolated preparations of rabbit gastric fundus and jejunum.

1. Pharmacological effects of delta-aminolaevulinic acid (ALA), protoporphyrin IX and haemin were examined in isolated preparations of rabbit jejunum and gastric fundus suspended in oxygenated Ringer-Locke solution at pH 7.0. 2. In jejunal preparations, delta-aminolaevulinic acid (3.0-4.5 mM), protoporphyrin IX (1.1-2.2 mM) and haemin (3.0-4.5 mM) dose-dependently reduced the amplitude of contractions and increased resting length. Pretreatment with prazosin (10(-7) M) inhibited effects produced by delta-aminolaevulinic acid (3 mM) and protoporphyrin IX (1.1 mM) but not those of haemin (3 mM). 3. In fundic preparations, dose-dependent contracture occurred in response to delta-aminolaevulinic acid (0.1-3.0 mM) protoporphyrin IX (0.1-2.2 mM) and haemin (0.6-6.3 mM). Effects qualitatively resembled those of noradrenaline (0.1-0.4 microM). Prazosin (10(-7) M) attenuated these effects, depressing the maximum response and causing a rightward shift of the concentration-response curves. 4. It is concluded that actions of delta-aminolaevulinic acid at alpha 1-adrenoceptor sites are unlikely to be related to the autonomic neuropathy of acute porphyria. Its in vitro effects occurred only at comparatively high concentrations and were mimicked by protoporphyrin IX and haemin. It is suggested that ALA is more likely to modify autonomic functions by an indirect action, since it is known at low dose levels to influence GABA-ergic functioning.

Aminolevulinic Acid↗
PubMed1990

The mauve factor of porphyria, 3-ethyl-5-hydroxy-4,5-dimethyl-delta-3-pyrroline-2-one: effects on behaviour of rats and mice.

The monopyrrole, 3-ethyl-5-hydroxy-4,5-dimethyl-delta 3-pyrroline-2-one (HPL), was given by intraperitoneal injection to rats (0.65 mmol/kg) and to mice (0.98 and 1.95 mmol/kg). Behaviour of the rats was assessed for 1.5 hr after injection by monitoring their spontaneous activity, while behaviour of the mice was examined by ethological procedures during dyadic encounters over a 5 min. period at 50-60 min. following injection. Activity of the rats, once habituated to the cage, was reduced by HPL. No other abnormalities were discernible. In mice, HPL at 1.95 mmol/kg increased the frequency of "head twitch" and evoked a smaller increase of "backward locomotion". There were no changes in overall agonistic, social or non-social behaviour in the HPL treated mice. Plasma concentrations of HPL in mice treated with the highest dose level amounted to 0.3 +/- 0.1 mmol/l, many-fold above its plasma concentrations during acute porphyric attacks in man. It thus appears that in rodents HPL has slight behavioural activity, but that it is unlikely to play any significant role in the psychiatric disturbances of acute porphyria.

Animals↗
PubMed1990

LHRH analogue treatment for the prevention of premenstrual attacks of acute porphyria.

We have assessed the value of suppressing ovulation with the luteinizing hormone releasing hormone (LHRH) analogue buserelin in seven patients experiencing crises of acute intermittent porphyria related to the menstrual cycle. Clinical course, plasma oestradiol and progesterone levels, and urinary porphyrin and precursor excretion were monitored over a baseline period of approximately one year, and then for a similar period on buserelin treatment. There was a trend towards clinical improvement on buserelin therapy. The median number of attacks fell from seven during the baseline period to three on treatment (p = 0.06). The response to buserelin varied considerably, with those patients in whom the association between baseline attacks and the menstrual cycle was strongest gaining the most benefit. All patients became amenorrhoeic with suppression of plasma oestradiol and progesterone levels. Urinary delta-aminolaevulinic acid and total porphyrin excretion fluctuated widely both before and during treatment. Our experience indicates that ovulation suppression may be of value in the management of young women in whom recurrent attacks of porphyria are related to the menstrual cycle.

Acute Disease↗
PubMed1990

Role of stereotactic radiosurgery with a linear accelerator in treatment of intracranial arteriovenous malformations and tumors in children.

Between 1986 and 1988, 16 children were treated for 10 arteriovenous malformations and 6 recurrent intracranial tumors with stereotactic radiation therapy using a modified Clinac 6/100 linear accelerator. The median age of our patients was 10.5 years. For the group with arteriovenous malformation, follow-up ranged from 6 months to 37 months (median was 20 months). No patient bled during the follow-up period. Five of eight patients with follow-up longer than 12 months have achieved complete obliteration of their arteriovenous malformation by angiogram. The four remaining patients who have not achieved a complete obliteration are awaiting their 2-year posttreatment angiogram. The other patient has been treated within the year and have not yet been studied. Five of the six recurrent tumor patients are alive with a median follow-up of 8 months. The remaining patient was controlled locally, but he died of recurrent disease outside the area treated with radiosurgery. The radiographic responses of these patients have included three complete responses, two substantial reductions in tumor volume (greater than 50%) and one stabilization. Despite previous radiotherapy, there have been no significant complications in these patients. We conclude that stereotactic radiation therapy using a standard linear accelerator is an effective and safe technique in the treatment of selected intracranial arteriovenous malformations and tumors in children. In addition, stereotactic radiosurgery may have unique applications in the treatment of localized primary and recurrent pediatric brain tumors.

Adolescent↗
PubMed1990

[Harvey Cushing: neurosurgeon and artist].

Harvey Cushing was a man of many talents. He was a skilled, surgeon, scientist, author and bibliophile. In addition, he was an accomplished artist for both medical non-medical subjects. In this paper, we present three surgical drawings of Dr Cushing's that are representative of the nearly one hundred drawings we have thus far found with his operative notes in the Peter Bent Brigham Archives. We will also discuss Cushing's non-medical art, some of the best of which is of the French countryside.

Art↗
PubMed1989

Controlled trial of haem arginate in acute hepatic porphyria.

A double-blind study comparing placebo and haem arginate was conducted in 12 patients with acute intermittent porphyria. 2 days after admission in attack patients were randomised to receive intravenous haem arginate 3 mg/kg per 24 h for 4 days or placebo. 9 patients were readmitted with a further attack and were given the alternative treatment. Before randomisation the paired attacks were of similar severity with respect to urinary porphobilinogen (PBG) excretion and clinical manifestations. With haem arginate the median PBG excretion of the 9 patients with two attacks (normal range 0-16 mumol per 24 h) fell significantly from 332 mumol per 24 h (range 137-722) on admission to a median lowest level of 40 (range 22-105). On placebo, median PBG excretion was 382 (range 196-542) on admission, falling to 235 (range 128-427). Median duration of admission after the start of treatment was 11 days (range 2-28) for placebo and 8 days (3-26) for haem arginate. Median total analgesic requirement between the start of treatment and discharge was 8150 mg pethidine equivalents (range 0-17,650) with placebo versus 6425 (range 50-20,650) with haem arginate. Phlebitis occurred in 5 patients on haem arginate and in 2 on placebo. Haem arginate effectively reduces porphyrin precursor overproduction in the acute porphyric attack but this reduction is not accompanied by striking resolution of the clinical manifestations of the attack.

Acute Disease↗
PubMed1989

The development of neurosurgical techniques: the postoperative notes and sketches of Dr. Harvey Cushing.

In the early development of American neurosurgical techniques, Harvey Cushing is often considered the founding father. As an accomplished artist and prolific writer his original operative sketches and detailed notes at the Peter Bent Brigham Hospital (1912-1932) are now being explored as early documentation of this pioneering surgeon's development of a field. We present four brain tumor cases with his unpublished sketches and direct quotations to illustrate both the trials and tribulations of those times and Cushing's innate surgical genius.

Brain Neoplasms↗
PubMed1989

Cushing and epilepsy surgery: two successfully treated cases with long-term follow-up.

Two of Dr. Harvey Cushing's patients who were successfully treated surgically for epilepsy are presented to illustrate his understanding of the problem. Both cases include his operative sketches and long-term follow-up, one includes the patient's recent brain computed tomography scan and autopsy specimen. Cushing's operative sketching habits and their importance are discussed.

Epilepsy↗
PubMed1989

Haem biosynthesis in the unconjugated hyperbilirubinaemias: observations in the Gunn rat model.

Disturbances of the enzymes of haem biosynthesis have been reported in patients with unconjugated hyperbilirubinaemia. We have examined the excretion of haem precursors in the Gunn rat which suffers from severe unconjugated hyperbilirubinaemia. In urine, levels of aminolaevulinic acid and total porphyrin were significantly reduced when compared to controls. In feces both coproporphyrin and protoporphyrin levels were reduced in Gunn rats, the former being more affected. Blood porphyrin levels in control and Gunn rats were similar.

Aminolevulinic Acid↗
PubMed1989

Therapy of the acute porphyrias.

In the management of acute porphyria it is essential to be aware of the potential for many drugs to induce porphyrin synthesis and thus precipitate the acute porphyric crisis. In this review, lists of drugs unsafe and safe for use in the porphyrias are presented. In addition, therapeutic regimens are described which are appropriate to the porphyric subject. These include the use of high carbohydrate intake and the intravenous infusion of haem arginate.

Dietary Carbohydrates↗
PubMed1989

Acute intermittent porphyria in two patients on anticonvulsant therapy and with normal erythrocyte porphobilinogen deaminase activity.

1. Acute intermittent porphyria (AIP) is sometimes termed a 'pharmacogenetic' disease. patients with genetic deficiency of the enzyme porphobilinogen deaminase are liable to develop acute attacks of porphyria if exposed to a variety of drugs. 2. Two patients are reported who had no evidence of deficiency of erythrocyte porphobilinogen deaminase yet developed typical attacks of AIP while on anticonvulsant therapy. 3. Normal activity of erythrocyte porphobilinogen deaminase does not completely exclude porphyria. 4. Acute porphyria should be suspected if clinical deterioration occurs during therapy with anticonvulsants, or other porphyrinogenic drugs, even in the absence of an underlying genetic defect in haem synthesis in peripheral blood cells.

Adolescent↗
PubMed1989

Growth stimulation of T47D human breast cancer cells by the anti-progestin RU486.

Our laboratory has previously reported that physiological levels of progestins stimulate growth of the human breast cancer cell line T47D. We have also determined that the antiprogestin RU486 inhibits this stimulation. Here we present the unexpected finding that RU486 alone also stimulates growth of these breast cancer cells. Thus, RU486 exhibits both antagonist and agonist-like activity, in a manner somewhat reminiscent of the antiestrogen tamoxifen. To our knowledge, this is the first report of stimulation of breast cancer growth by RU486.

Breast Neoplasms↗
PubMed1989

Effects of progestins, estrogens, and antihormones on growth and lactate dehydrogenase in the human breast cancer cell line T47D.

We have previously reported progestin stimulation of growth and lactate dehydrogenase (LDH) in the human breast cancer cell line T47D. Our further findings now show that growth stimulation by progestins occurs in a dose-responsive manner at physiological concentrations and is inhibited by the antiprogestin RU486. 17 beta-Estradiol (E2) also stimulates proliferation and LDH, and these stimulations are inhibited by tamoxifen. In addition, tamoxifen alone slightly stimulates proliferation. Surprisingly, RU486 also inhibits stimulation by E2. Thus, RU486 acts not only as an antiprogestin, but also as an antiestrogen. While combined promegestone (R5020) and E2 substantially stimulate proliferation, when RU486 is added to this combination it does not further inhibit, but leads to enhanced stimulation. However, the same addition of RU486 to combined E2 and R5020 diminishes LDH stimulation. This suggests that LDH stimulation and growth stimulation are dissociated. Finally, tamoxifen inhibits growth stimulation by combined R5020 and E2, but addition of the antiprogestin RU486 to this combination does not lead to a further inhibition of proliferation. Even so, this same combination reduces LDH levels to control values, further suggesting that stimulation of growth and LDH are dissociated. All of these findings occurred in the absence of the estrogenic pH indicator phenol red. These results emphasize the potential of LDH as an end point for studying the mechanism of female steroid hormone action. They also reveal antiestrogenic activity in RU486. Further, they shed light on the interaction among estrogens, progestins, antiestrogens, and antiprogestins in their effects on growth. Further understanding of this complex interplay may be helpful in treatment of human breast cancer.

Breast Neoplasms↗