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Biomedical subjects

J Ford

Publications and source records attributed to J Ford.

At least 163 records · Page 9Linked to original sources

A phase II study of sequential methotrexate and fluorouracil in advanced colorectal cancer.

Twenty-nine patients with advanced colorectal cancer were treated with methotrexate (MTX) 200 mg/m2 followed 1 h later by fluorouracil (FU) (1000 mg/m2) and 24 h later by oral leucovorin 20 mg every 6 h for six doses. The cycle was repeated every 2 weeks. Among the 25 evaluable patients there were 2 complete responses (confirmed by liver scan) and 5 partial responses. Although hematological toxicity was mild, there were four episodes of nonfatal sepsis. The majority of patients developed an erythematous scaly rash on the palms and soles plus eye irritation after six courses of chemotherapy. In addition, the sequential MTX-FU had to be discontinued in 6 of the 7 responders because of (a) severe chills, (b) severe hyperpigmentation, or (c) neurologic complications (ataxic gait or disorientation). These results indicate that this sequential MTX-FU has modest activity in colorectal cancer but is associated with moderately severe toxicity. Only randomized trials of FU alone versus sequential MTX-FU can determine whether sequential MTX-FU has a therapeutic advantage over FU alone in the treatment of advanced colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

The results of a selective surgical policy on the cognitive abilities of children with spina bifida.

A cohort of spina-bifida children born between 1973 and 1978 and subjected to selection for surgery was divided into those who met specific physical criteria at birth and were offered immediate treatment, and those who had delayed treatment because of adverse criteria. There was a significantly higher level of intelligence among children treated immediately but a fifth of those given delayed treatment had normal levels of intelligence. There were negligible differences in intelligence between the children given delayed treatment and an unselectively treated series of children born between 1964 and 1966, suggesting that postponing surgery for a period does not necessarily have a disastrous effect upon ability.

Child↗

Selective surgical management of neural tube malformations.

The physical characteristics of 49 children with spina bifida cystica, survivors of a group subjected to selection for early surgery are compared with 39 children alive from an earlier unselected series, born in the 1960s, and reviewed retrospectively. Sixteen children were also studied in whom the initial decision not to operate had been followed by survival and subsequent treatment. Children selected for initial surgery have a significantly lower mortality than those not selected and their mobility at 5 to 7 years of age is better, although only marginally so compared with the unselected group. Selection does not decrease the need for shunt treatment of the associated hydrocephalus. None of those not initially selected for surgery have normal faecal or urinary continence, whereas 35% of the selected in group have normal continence and urinary tracts. Children treated immediately have significantly higher degrees of intelligence than both the unselectively treated and those whose treatment was delayed but a fifth of the latter group were intellectually normal. There were only small differences in intelligence between children given delayed treatment and those unselectively treated, suggesting that postponing surgery does not necessarily have a deleterious effect on ability.

Cerebrospinal Fluid Shunts↗

Self cleavage of a precursor RNA from bacteriophage T4.

We found that a precursor of an RNA molecule from T4-infected Escherichia coli cells (p2Spl; precursor of species 1) has the capacity to cleave itself in a specific position. This cleavage is similar to a cleavage carried out by the aid of a protein, RNase F, that has been previously identified. This cleavage could lead to the maturation of an RNA (species 1) found in T4-infected E. coli cells. The reaction is time and temperature-dependent and is relatively slow as compared to the protein-dependent reaction. It requires at least a monovalent cation and is aided by non-ionic detergents. In the absence of detergent the cleavage can occur but at a reduced rate. The substrate does not contain hidden nicks and a variety of experiments suggest that it does not contain a protein. Moreover, we found no indication that the cleavage is due to contaminating nucleases in the substrate or in the reagents. The intact secondary and tertiary structures of the molecule are necessary for the cleavage to occur. The finding of a self cleaving RNA molecule has interesting evolutionary implications.

Base Sequence↗

Increased HbF in sickle cell anemia is determined by a factor linked to the beta S gene from one parent.

Members of 7 large families, containing 20 patients with sickle cell anemia (SS) characterized by high levels of fetal hemoglobin (HbF), were studied using immunofluorescence to count F cells and a radioimmunoassay to measure small amounts of HbF. In five of these families, one of the sickle cell trait (AS) parents had a much higher HbF and F-cell count than the other; in one family, both parents had a marked increase in HbF and F cells; in the remaining family, HbF and F cells were at borderline values in both parents. Seven of 14 AS siblings, but only 1 of 8 normal hemoglobin (AA) siblings, also had HbF and F-cell counts above the "normal" range. It seems that a factor for increased F cells, linked to the beta S gene of one parent, is segregating in these families and is responsible for the greatly increased HbF and F cells in the SS subjects. HbF per F cell in AS parents and siblings was the same as that of normal AA subjects, whereas in the SS offspring it was greatly increased, suggesting that it was the result of marrow hyperplasia associated with their hemolytic anemia. The similarity of this "increased F-cell gene" to heterocellular hereditary persistence of fetal hemoglobin (HPFH). Swiss type, is discussed, and it is suggested that it may control the persistent synthesis of HbF in sickle cell anemia by its presence in early infancy.

Adolescent↗

Intestinal stomal dilatation.

Dilatation of 23 surgically created gastrointestinal tract stomata in 21 patients has been performed using angioplasty techniques. A success rate of 44% was achieved in nine patients with gastric stapling and Marlex mesh wrapping of the greater curve stoma. In 13 patients with gastric stapling, and either sutured gastro-gastrostomy or roux-en-y gastro-jejunal bypass, a success rate of 77% was achieved. In one patient with a jejunostomy, stenosis dilatation was also successful.

Angioplasty, Balloon↗

Serum cortisol concentrations in gilts and sows housed in tether stalls, gestation stalls and individual pens.

Three experiments were conducted to determine whether housing in tether stalls, gestation stalls or individual pens imposes a stress upon gilts and sows. Changes in serum cortisol concentrations were used as the indicator for stress. In the first experiment, gilts were placed in tether stalls and individual pens to determine cortisol concentrations after tethering and to see if this response was different from gilts that were previously tethered for two weeks. In the second experiment, gilts were tethered in order to determine if penning in tether stalls altered the circadian rhythm of cortisol. In the third experiment, breeding sows were placed in tether stalls, gestation stalls or individual pens to determine if a ten-hour profile of cortisol concentrations were altered and if such housing affected a sow's response to transfer to farrowing crates. The results indicate that the initial response to tethering varied among gilts and sows and this variation appeared to be due to previous penning and human handling experiences. When tethering was stressful, acclimation required up to four days. However, once acclimated, tethering resulted in higher morning concentrations which may be associated with the greater activity that occurs at this time. Housing in tether stalls, gestation stalls or individual pens was not a stress for breeding sows and did not alter sows' responses to transfer into the farrowing crate.

Animals↗

RNA processing: new mutants that affect endonucleolytic processing of RNA.

A strain of Escherichia coli carrying the rne-3071 mutation that affects the RNA processing enzyme ribonuclease E, was mutagenized, and double mutants deficient in RNA processing were isolated. The isolation was based on the appearance of a particular RNA precursor molecule upon infection of an rne mutant with a specific bacteriophage T4 deletion strain. From one of the double mutants the rne mutation was removed, and the new single mutant, designated rng, was examined. In this mutant the maturation of host RNA as well as of bacteriophage T4 RNA is affected. The effect of the rng mutation on RNA synthesis is unique and can be distinguished from the effects of the other established mutations in RNA processing. The effects of the rng mutation can be recognized in vivo and in vitro.

Coliphages↗

Progressive supranuclear palsy: clinical features and response to treatment in 16 patients.

Among 415 patients with parkinsonism, 16 (3.9%) had findings of progressive supranuclear palsy (PSP). This report reviews the clinical features and response to drug therapy in those 16 patients. Anticholinergic drugs failed to benefit any of the 5 patients treated, while presynaptic dopaminergic drugs (Sinemet or amantadine) were beneficial in only 5 of 22 patient trials. Alternatively, dopamine agonists (bromocriptine and pergolide) caused improvement in 9 of 14 patient trials despite the fact that all but 1 of these patients had previously failed to respond to presynaptic dopaminergic drugs. Dopamine agonists such as bromocriptine and pergolide may be useful in some patients with PSP.

Aged↗

Blepharospasm and orofacial-cervical dystonia: clinical and pharmacological findings in 100 patients.

We evaluated prospectively 100 patients, the largest reported series, with blepharospasm and orofacial-cervical dystonia, or Meige syndrome. The mean age at onset was 51.7 years, and 81% presented between the ages of 40 and 70. Women outnumbered men three to two. Blepharospasm was the initial symptom in 58 patients, but only 23 had involuntary movements localized to the orbicularis oculi. Sixty-one patients had the complete syndrome, blepharospasm and oromandibular dystonia, and 60 had neck or generalized dystonia in addition to the orofacial movements. Twenty-one patients with spasmodic dysphonia were included; in 12 of these patients, spasmodic dysphonia was part of the complete (Meige) syndrome, and 16 of these patients had neck or generalized dystonia or essential tremor. An organic cause of Meige syndrome is supported by a high correlation with essential tremor and other movement disorders and by positive family history in some patients. Response to medication was inconsistent, but 69% of patient trials resulted in some improvement; in 22% the benefit was marked and persistent. Tetrabenazine, lithium, and trihexyphenidyl were most useful for the treatment of oromandibular dystonia, and clonazepam was useful in some patients with blepharospasm.

Adult↗

Manipulation of P3 latency: speed vs. accuracy instructions.

Twelve young female subjects were presented with a series of horizontal line-pairs of same or different length in a two-alternative, forced-choice RT task, with 60 of each type pair in each block of trials. In one block (Easy) lines differed by 30%, in another block (Difficult) lines differed by 7%. Subjects were first given 60 practice trials with the Easy discrimination and with the instruction that speed and accuracy should be emphasized equally. For the next block of trials, accuracy was emphasized with a monetary bonus for accurate performance. Finally, in the last block of trials, speed was emphasized with a monetary bonus for speedy performance. Additionally, a penalty was incurred for RTs that exceeded a criterion level based on each individual subject's performance. The order of Easy and Difficult discrimination blocks was maintained within a subject but balanced across subjects. From the latency-adjusted P3s recorded from Pz, we obtained P3 latencies, amplitudes and single-trial P3 latency/RT correlations. RT to correct and incorrect trials and error data were also collected. P3 was considerably larger during the Speed than Accuracy conditions. The single-trial P3 latency/RT correlation was higher in Speed than in Accuracy runs. RT was 235 msec faster and P3 was 40 msec earlier during the Speed than during the Accuracy runs. On the other hand, discrimination difficulty delayed P3 and RT about equally, 28 and 43 msec respectively. This pattern suggests that speed instructions and discrimination difficulty affect stimulus processing time and response production time differently.

Adult↗

The XX male. Clinical and theoretical aspects.

A male patient attending a fertility clinic was recognized as having an XX chromosomal constitution. The clinical and theoretical aspects of the XX male are discussed and note is made of some improvement in the understanding of the condition with the determination of the H-Y status of these individuals.

Adult↗