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Biomedical subjects

D Phillips

Publications and source records attributed to D Phillips.

At least 73 records · Page 4Linked to original sources
PubMed1991

Preparative, analytical and fluorescence spectroscopic studies of sulphonated aluminium phthalocyanine photosensitizers.

Fluorescence spectroscopic studies were carried out on aluminium phthalocyanine with defined numbers (mono, di, tri and tetra) of sulphonate groups. Selective sulphonation was achieved using one of two synthetic methods to prepare a mixture of components which were separated using reverse-phase liquid chromatography. Fluorescence lifetimes were measured in methanol and buffer solution using time-correlated single-photon counting with picosecond laser excitation; the lifetime shows little variation with the number of sulphonate groups. Using steady state excitation, fluorescence quantum yields were determined for the tetrasulphonated component (phi F = 0.51) and, for comparison, unsulphonated aluminium phthalocyanine.

Indoles↗
PubMed1991

Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl]-2-imidazolidinones.

The synthesis and biological properties of a novel series of selective calcium-independent phosphodiesterase inhibitors are described. These compounds also inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit efficacy in preclinical models of antidepressant activity in mice, such as reducing immobility in the forced-swim test and reversing reserpine-induced hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds studied.

Animals↗
PubMed1991

The detection of phthalocyanine fluorescence in normal rat bladder wall using sensitive digital imaging microscopy.

The ability to detect photosensitisers in tissue at a microscopical level is important when studying photodynamic therapy (PDT) in both normal and malignant tissue. We have studied the fluorescence distribution of aluminium sulphonated phthalocyanine (A1SPc) in the normal rat bladder using a cooled CCD (charge coupled device) imaging system with computerised image processing. This system makes it possible to carry out a quantitative assessment of photosensitiser fluorescence in the various layers of the bladder wall. The highest fluorescence intensities were obtained within 1 h of intravenous administration but there was little selectivity of uptake between layers. A1SPc was eliminated from the deeper muscle layers more quickly than from the superficial layers of the bladder wall so that by 24 h a 4:1 ratio of fluorescence intensity was apparent which persisted at least until 72 h, although the absolute amount of photosensitiser declined. Following irradiation by red light (675 nm), photobleaching of the sensitiser in the deeper layers further increased this ratio. Direct absorption of A1SPc by the bladder wall following intravesical administration proved unreliable.

Administration, Intravesical↗
PubMed1991

Distribution and photodynamic effect of disulphonated aluminium phthalocyanine in the pancreas and adjacent tissues in the Syrian golden hamster.

Necrosis of small volumes of tumour tissue with photodynamic therapy (PDT) can be achieved relatively easily. For this to be clinically relevant, it is essential to know what the same treatment parameters do to adjacent normal tissues into which the tumour has spread. For pancreatic cancers, local spread to vital structures is common. We have studied chemical extraction, microscopic fluorescence kinetics and photodynamic effects of disulphonated aluminum phthalocyanine (AlS2Pc) in normal pancreas and adjacent tissues in hamsters. Chemical extraction exhibited a peak duodenal concentration of AlS2Pc 48 h after sensitisation, with levels much higher than in stomach and pancreas. With microscopic fluorescence photometry highest levels were seen in duodenal submucosa and bile duct walls 48 h after photosensitisation. Pancreatic ducts, duodenal mucosa and gastric mucosa and submucosa exhibited intermediate fluorescence with relatively weak fluorescence in pancreatic acinar tissue and the muscle layer of the stomach. As expected, on the basis of fluorescence intensity and chemical extraction studies, the duodenal and bile duct wall were the most vulnerable tissues to photodynamic therapy. When the dose of 5 mumol kg-1 of sensitiser was used, duodenal perforations, gastric ulcers and transudation of bile from the bile duct occurred. However, the lesions in the stomach and bile duct healed without perforation or obstruction, so only the duodenum was at risk of serious, irreversible damage. Using a lower dose of photosensitiser markedly reduced damage.

Animals↗
PubMed1991

The objective assessment of nasal patency.

Nasal patency was measured by five techniques in 24 subjects and the results compared. In addition three pulmonary parameters were measured as well as height and weight. Nasal resistance to airflow measured by active anterior rhinomanometry was found to be highly correlated with peak nasal inspiratory flow rate. Other correlations were also noted. Peak nasal inspiratory flow was itself highly correlated with pulmonary peak expiratory flow rate as well as with several other parameters. The possible reasons for these correlations are discussed in terms of fluid mechanics.

Adult↗
PubMed1991

Comparison of distribution and photodynamic effects of di- and tetra-sulphonated aluminium phthalocyanines in normal rat colon.

We have previously reported photodynamic therapy of normal rat colon using aluminium sulphonated phthalocyanine (AISPc). In that study, the AISPc used was a mixture of phthalocyanines of different degrees of sulphonation. Phthalocyanines of defined degrees of sulphonation have recently become available and we compared the distribution of the di- and tetra-sulphonates (AIS2Pc and AIS4Pc) in rat colon and colon wall structures employing both chemical extraction and fluorescence photometry using a charge coupled device imaging system. Also, the photodynamic effects produced by these components in rat colon were compared at various times after photosensitization. After intravenous photosensitizer administration using equimolar doses, the concentration of AIS2Pc in colon fell off more rapidly with time than AIS4Pc. Differences were noted in the microscopic distribution of these compounds, with the di-sulphonate exhibiting peak fluorescence in colon wall structures by 1 h after photosensitization, while mucosal fluorescence with the tetra-sulphonate peaked at 5 h. Fluorescence was also lost from the colon wall much more slowly with the tetra-sulphonate, which tended to be retained in the submucosa. Maximum photosensitizing capability was seen at 1 h with AIS2Pc and no lesions could be produced with photodynamic therapy at 1 week, with up to 5.65 mumol/kg. With AIS4Pc (5.65 mumol/kg), while no lesions could be produced with light treatment at 1 h, photodynamic therapy at 1 week produced lesions only slightly smaller than those produced with treatment at 48 h (the time of maximum effect), and significant photosensitization was present at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1991

Autosomal dominant inheritance of autoantibodies to thyroid peroxidase and thyroglobulin--studies in families not selected for autoimmune thyroid disease.

Recently the tendency to produce autoantibodies to thyroid peroxidase (TPO Ab) and thyroglobulin (Tg Ab) was shown to be inherited as an autosomal dominant characteristic in women but not in men. Because of potential bias in this study which was carried out in families with autoimmune thyroid disease (AITD), the inheritance of thyroid autoantibodies has been evaluated in 49 families unselected for autoimmune thyroid disease. Among these families (24 with facioscapulohumeral disease, 10 with Friedreich's ataxia, and 15 with schizophrenia) the prevalences of TPO Ab and Tg Ab were 27.8% and 26.7%, respectively, in women and 9.2% and 11.7%, respectively, in men. In 40 families where one or more individual had TPO Ab and/or Tg Ab, segregation analysis showed that the tendency to make antibodies was consistent with a Mendelian dominant trait in women but not in men. In young women, however, the prevalence of both TPO Ab and Tg Ab increased with age, rising from 14% and 10%, respectively, at age 15-24 to 35% and 40% at age 35-44. As this is inconsistent with a simple dominant hypothesis, a further segregation analysis by age was carried out in the families unselected for thyroid disease together with 16 pedigrees with AITD previously studied and two additional large AITD families. The results of the combined analysis provided strong support for the hypothesis of dominant inheritance but also showed significant reduction in gene expression among women aged 15-24 yr.

Adolescent↗
PubMed1991

Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein.

We studied a series of 64 patients with sensory +/- motor peripheral neuropathies by comparing clinical and physiologic features to serum antibody reactivity against compounds containing sulfated carbohydrate moieties. We determined antibody reactivity by an enzyme-linked immunosorbent assay (ELISA) using purified glycolipids and glycoproteins as antigens, and we used high-performance thin-layer chromatography and Western blotting to test the specificity of results. Twelve patients with high titers of IgM antibodies directed against the myelin-associated glycoprotein (MAG) had sensory-motor polyneuropathies with physiologic evidence of demyelination. IgM antibody reactivity to MAG was associated with an IgM serum M protein in five patients. Eight other patients, most with sensory greater than motor polyneuropathies, had high titers of antibody reactivity to sulfatide but not of IgM to MAG. Two had an associated IgM paraprotein. None of the patients with selective serum antisulfatide activity had predominantly demyelinating features on physiologic testing. We conclude that (1) high ELISA titers of antibodies to MAG may be more common than previously suspected in patients with chronic demyelinating sensory-motor neuropathies, and (2) the presence of high titers of antisulfatide antibodies in serum may provide clues to the pathogenesis of otherwise idiopathic, axonal, predominantly sensory neuropathies.

Adult↗
PubMed1990

New family of high-resolution ion exchangers for protein and nucleic acid purifications from laboratory to process scales.

A new family of polymer-based ion exchangers was tested for the purification of acidic and basic proteins on both the analytical and preparative scales. Protein-Pak HR series packings are available as strong cation (SP) and weak anion (DEAE) exchangers, allowing the development of a purification method regardless of the isoelectric point of protein. Three particle sizes, 8, 15 and 40 microns, are offered in scalable Advanced Purification (AP) glass columns or as bulk packings. The lower back pressures of the 15- and 40-microns packings compared to that of the 8-microns material allow rapid throughput of large volumes without exceeding the pressure limitations of the resin or the column. The capacity of the AP1 (100 mm x 10 mm) glass columns, containing these ion-exchange packings, is comparable to other ion-exchange columns. The resolution of mouse serum, plasmids, and a standard protein mixture was demonstrated and compared with the results obtained with other resin-based ion exchangers of similar particle size. Proteins were purified without significant loss of biological activity or mass.

Alkanesulfonates↗
PubMed1990

Altered operant behavior of adult rats after perinatal exposure to a 60-Hz electromagnetic field.

Rats were sham exposed or exposed perinatally to a 60-Hz electromagnetic field, 22 days in utero and the first 8 days post partum. Each of the 30 once-daily exposures was 20 h in duration. The electric component of the field was vertical 30 kV/m rms, and the magnetic field component was 100 microTG rms. Later, as adults, male rats were trained to emit an operant response when reinforced with food on a multiple, random-interval schedule. Exposed rats (N = 21) gradually came to respond at significantly lower rates than did sham-exposed controls (N = 20). This finding was confirmed and extended in a second, independently performed experiment. After a sequence including operant conditioning followed by experimental extinction of responding and then by a suspension of conditioning and finally by more than a month of reconditioning, slower rates of responding were found to persist in the adult animals. The evidence of altered behavior several months after combined, fetal-neonatal exposure to an electromagnetic field presents an interesting contrast with other findings: Field-exposed rats did not differ from sham-exposed rats in terms of body mass, physical appearance, grossly observed activity level, or incidence of disease.

Animals↗
PubMed1990

Selective necrosis in dimethylhydrazine-induced rat colon tumors using phthalocyanine photodynamic therapy.

Photodynamic therapy is a relatively new method for the local destruction of tumors based on the administration of a photosensitizing agent that is retained in tumors and then activated to produce cytotoxic agents following irradiation with light. The selective retention of photosensitizers by dimethylhydrazine-induced colonic tumors over adjacent normal tissue is small (2:1, tumor to normal), making the possibility of producing selective tumor necrosis with total sparing of normal tissue difficult. Colonic cancers and adjacent normal colon were treated with the same light doses from an argon-pumped dye laser 48 h after intravenous injection of 0.5 or 5 mg/kg of the photosensitizer, aluminum-sulfonated phthalocyanine. There was little difference between the amount of necrosis in the tumor and the adjacent normal colon if the injected dose of photosensitizer was 5 mg/kg. However, at the lower dose of 0.5 mg/g, up to 2 mm of necrosis could be produced in the tumor without damaging the normal colon. In vivo fluorescence measurements showed that the photosensitizer was photodegraded during irradiation. This was confirmed by in vitro fluorescence scans of the normal colon after irradiation; the fluorescence from the photosensitizer was lowest at the point of irradiation. It is postulated that at low dosage, selective necrosis can occur because the photosensitizer is photodegraded in the normal colon before a threshold photodynamic dose is reached, whereas in tumor containing twice as much photosensitizer, a photodynamic threshold dose can be achieved and necrosis produced.

1,2-Dimethylhydrazine↗
PubMed1990

"Isolated" elevation of alkaline phosphatase: significance in hospitalized patients.

The significance of alkaline phosphatase (AP) elevation with otherwise normal transaminase and bilirubin values remains unclear. We evaluated the clinical outcome of hospitalized patients with an "isolated" AP elevation. Eighty-seven inpatients with isolated AP elevation were identified during February 1984 and followed for 1 year. Forty-five of 87 patients had normalization of AP during the follow-up period, usually within 1-3 months. The most common diagnoses in this group were congestive heart failure in nine, benign bone disease in six, and treatable malignancy in three patients. Twelve patients had no apparent explanation for the transient rise of AP. Persistent AP elevations were noted in 42 patients--14 of whom had terminal malignancies. Clinically obvious life-threatening diagnoses were made in 24 of the patients with persistent AP elevation. The etiology of AP elevation remained enigmatic in seven patients: two died, four are stable during 1 1/2-3 years of follow-up, and one patient was found to have metastatic carcinoma 17 months later. If the initial AP was greater than 1 1/2 times normal, there was a higher likelihood of persistent elevation (68% vs. 41%, p less than 0.05). Isolated elevations of AP in inpatients may be associated with a variety of medical illnesses and often normalize within months. If the AP elevation is persistent, there is usually a clinically obvious diagnosis. A reasonable approach to such patients is a careful history, physical exam, and routine lab studies to detect obvious diagnoses, followed by repeat enzyme determination at 1-3 months.

Alkaline Phosphatase↗
PubMed1990

Granuloma gluteale infantum: case report and review of the literature.

Granuloma gluteale infantum, a benign granulomatous eruption involving the gluteal region, histologically shows a nonspecific dermal inflammatory infiltrate composed of neutrophils, lymphocytes, histiocytes, plasma cells, and eosinophils. It is important to recognize this condition, as it may clinically simulate a neoplastic process. It arises as a complication of primary irritant diaper dermatitis, however, and typically resolves without treatment.

Biopsy↗
PubMed1990

Autosomal dominant transmission of autoantibodies to thyroglobulin and thyroid peroxidase.

The inheritance of autoantibodies to thyroglobulin and thyroid peroxidase (thyroid microsomal antigen) has been reevaluated with newly developed ultrasensitive assays that depend on the direct interaction between antibody and radiolabeled antigen. In a study of 16 families with autoimmune thyroid disease, autoantibodies to thyroid peroxidase (TPO) were found to be inherited as a dominant Mendelian trait in females with reduced penetrance in males. Similar results were obtained with thyroglobulin (Tg) autoantibodies. Genetic linkage analysis of the loci for TPO and Tg autoantibodies with 28 polymorphic serological markers (including HLA and Gm allotypes) was carried out in 9 families. LOD scores for some serological markers (such as Gm) were uninformative, but linkage with other markers, notably the HLA antigens -A, B, -DR, -DQ, and BF on chromosome 6, could be excluded. Further studies using a comprehensive panel of gene probes to analyze DNA from families with autoimmune thyroid disease should permit the localization of the gene cluster responsible for regulating the ability to produce autoantibodies to TPO and Tg in man.

Adolescent↗
PubMed1990

Physician controlled drug records.

A general understanding of the laws and regulations of the applicable standards of conduct in the use of controlled drugs will assist every physician in recognizing potential problems and dealing with them in an effective manner without the risk of disciplinary action. The investigators for the Arkansas State Medical Board routinely check controlled drug prescribing, ordering and prescribing habits by random periodic surveys throughout the state. Records that accurately reflect a diagnostic assessment of a medical condition and complete accountability for controlled drugs administered, dispensed or prescribed would substantially reduce the likelihood of excessive prescribing for other than legitimate medical purposes.

Arkansas↗
PubMed1990

Withdrawal from maternity care. A comparison of family physicians in Ontario, Canada, and the United States.

To determine the relative importance of factors influencing the withdrawal of family physicians from maternity care, two studies, one done in Ontario, Canada, and the other done in the United States, were compared. The proportion of residency-trained family physicians who provide maternity care at the initiation of their careers and the proportion who have given up maternity care are nearly identical in the United States and Canada. Both studies found that about one half of the family physicians who currently provide maternity care were giving consideration to stopping. The reasons underlying this withdrawal were multifactorial. Malpractice issues were the predominant concern of United States family physicians, but the data from the studies indicate that other issues, such as interference with lifestyle and office practice and the effect of attitudes of obstetricians, should not be overlooked.

Adult↗
PubMed1989

Diurnal variation in vision after radial keratotomy.

We tested eight patients who had undergone radial keratotomy with regard to refraction, keratometry, corneal thickness, and intraocular pressure one to two weeks after surgery. Patients were examined immediately after eye-lid opening at 7:30 A.M. and again at 4:00 P.M. The contralateral eye was used as a control. The treated eye was 1.48 +/- 0.24 diopters (mean +/- S.E.M.) more hyperopic at the morning examination compared to the afternoon visit, whereas the control eye had an insignificant shift (0.16 +/- 0.06 diopters). The treated eye was significantly flatter (1.37 +/- 0.19 diopters) in the morning than in the afternoon when compared to the control eyes, which were only 0.11 +/- 0.09 diopter flatter. The intraocular pressure changed insignificantly in both the treated and control eyes (-0.5 +/- 0.53 mm Hg and -0.5 +/- 0.84 mm Hg, respectively). The mean morning corneal thickness was significantly greater (5.7%) than the afternoon thickness when compared to the controls (1.7% morning increase in thickness). These data suggest that diurnal variation in corneal thickness after radial keratotomy plays a role in diurnal variation of vision in the early postoperative period.

Adult↗