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Biomedical subjects

J Gilbert

Publications and source records attributed to J Gilbert.

At least 145 records · Page 8Linked to original sources

Penile agenesis: a fatal variation of an uncommon lesion.

Two male neonates (46XY karyotype) were born with a triad of penile agenesis associated with imperforate anus and complete absence of the median raphe. Both patients died of renal dysplasia and secondary pulmonary hypoplasia shortly after birth. This triad appears to be secondary to a lack of caudal mesoderm migration during month 1 of gestation, leading to severe developmental defects in the caudal axis. In all reported cases to date this triad of findings has been incompatible with extrauterine life.

Abnormalities, Multiple↗

Modified system outcome score and outcome index--method of monitoring patient care in a special care area.

A scoring system intended both to assess mortality risk and permit surveillance, evaluation, and comparison of medical care was developed in our surgical ICU. Five simple clinical indices of organ system failure were selected and weighted according to their statistically validated relationship to mortality, resulting in a daily System Outcome Score (SOS). Cluster analysis was used to divide the creation data set of 2,777 patients into suitable groupings of scores to predict mortality; the clustering was confirmed for reproducibility with a validation set of an additional 2,860 patients. Based on this validation of the scoring system, two computer-controlled patient care surveillance techniques were developed. The first involved the definition of three unfavorable SOS patterns evolving during the course of a patient's admission. Detection of one or more of these patterns, described by the acronym SDL, permits review of the care administered to the specific patient generating the pattern. A global assessment of care is achieved with the Outcome Index (OI), which relates overall mortality risk in the ICU to the actual mortality rate over a given time period. Effectiveness of care can then be compared between different time periods within the one unit or between different units with similar patient mix. The overall system offers the potential for a surveillance-based quality assurance system with widespread applicability.

Hospital Information Systems↗

Clinical monitoring of steatorrhoea in cystic fibrosis.

In 100 patients with cystic fibrosis the severity of steatorrhoea was assessed by three separate methods. Using chemical faecal fat assay as the gold standard, two other rapid and inexpensive methods were compared with it. The steatocrit method proved unreliable in our hands and gave little indication of the presence or severity of steatorrhoea. The more simple microscopy method was highly sensitive (97%) and only three of 80 patients with steatorrhoea were missed. All patients with severe steatorrhoea (greater than 60 mmol fat/day) were clearly demonstrated. The method is applicable to spot faecal samples and can readily be carried out on an outpatient basis. In centres where faecal fat assays are not available, the simple and cheap microscopic examination will give some indication of the response to enzyme treatment and may also help to identify non-compliant individuals.

Adolescent↗

Brain neurotransmitter changes in three patients who had a fatal hyperthermia syndrome.

The authors examined the autopsied brains from three patients who had a fatal hyperthermia syndrome. There was marked hypothalamic noradrenaline depletion in all three patients, severe brain choline acetyltransferase deficiency with nucleus basalis cell loss in two patients, and mild to moderate brain choline acetyltransferase loss in one patient. Striatal dopamine metabolite/dopamine ratio was below normal in two patients and not elevated, as would be expected after short-term neuroleptic administration, in the third. This suggests that reduced capability (aggravated by the cholinergic deficit) of the nigrostriatal dopamine system to respond adequately to stress and/or neuroleptic-induced receptor blockade may be important in the development and course of fatal hyperthermia syndrome.

Adolescent↗

Fourth ventricular schwannoma. Case report.

A schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described. A ventricular schwannoma has not previously been reported in the literature. The presenting clinical and radiographic features and the pathology of this tumor are summarized, and an explanation is sought for its unusual location.

Brain Neoplasms↗

Modes of inhibition of protein kinase C by triphenylacrylonitrile antiestrogens.

Protein kinase C (PKC) I (gamma), II (beta) and III (alpha) subspecies' activities are inhibited by three triphenylacrylonitrile (TPE) antiestrogens at micromolar concentrations. TPE 1 (having a p-hydroxy and a p-diethylaminoethoxy group on the 3-, and 3'- phenyl rings respectively) and TPE 2 (having a p-diethylaminoethoxy group on both the 3-, and 3'- phenyl rings) are competitive with the mechanism of activation by phosphatidylserine (PS). TPE 3 (having p-hydroxy groups on each of the three phenyl rings) is non-competitive with PS and inhibits the Ca2+- and PS-independent phosphorylation of protamine sulfate by PKC subspecies. This evidence suggests that PKC activity can be inhibited by different routes depending on the TPE structure: diethylaminoethoxy side chain-substituted TPEs (TPE 1 and 2) interact with PS as well as with the regulatory domain, whereas the trihydroxylated derivative (TPE 3) inhibits the enzyme by interacting with the catalytically active site.

Acrylonitrile↗

Fatal rhabdomyolysis and renal failure associated with hand, foot and mouth disease.

Fatal severe rhabdomyolysis and anuric renal failure developed in a young man who had contracted hand, foot and mouth disease during an epidemic of this disease. Viral studies implicated coxsackievirus A16 as the infecting agent. This appears to be the first reported case of rhabdomyolysis that was associated with hand, foot and mouth disease and infection with coxsackievirus A16.

Adult↗

Cerebellar [3H]inositol 1,4,5-trisphosphate binding is markedly decreased in human olivopontocerebellar atrophy.

We examined the behaviour of [3H]inositol-1,4,5-trisphosphate (IP3) binding in autopsied cerebellar and cerebral cortex of 10 neurologically normal controls and 8 patients with end-stage olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder characterized histologically by severe degeneration of Purkinje cells. [3H]IP3 binding to normal human cerebellar cortex was 6-15 times higher than in cerebral cortex. As compared with the controls, mean [3H]IP3 binding to cerebellar cortex was markedly reduced by 61% in the OPCA patients whereas levels were normal in frontal and occipital cortices. Since the Purkinje cell dendrite receives neuronal input from granule cells and climbing fibers utilizing glutamate and aspartate, respectively, as neurotransmitters, the reduced IP3 binding in OPCA cerebellar cortex may reflect a loss of Purkinje cells containing these excitatory amino acid receptors linked to the phosphatidylinositide second messenger system. Our data suggest that in humans, IP3 receptors may be highly localized to the Purkinje cell dendrite.

Adult↗

The outcome index. A method of quality assurance in the special care area.

A method of quality assurance for a surgical intensive care unit is described. A system outcome score is devised, incorporating only easily obtained objective components that reflect the likelihood of death. Through the use of a derived outcome index, the actual mortality rate is compared with the predicted mortality rate as a method of monitoring the quality of care provided. Subroutines exist to identify errors in data entry, to detect malicious interference in patient care, to add nonscoring components for the purposes of clinical studies, and to facilitate retrieval of a concise summary of the major events during the stay of every patient admitted to the intensive care unit.

Abstracting and Indexing↗

Detection of residues of chloramphenicol in crude extracts of fish and milk by tandem mass spectrometry.

The collision-induced dissociation mass spectrum, observed with a hybrid tandem instrument, of the ammonia chemical ionization protonated molecular ion of chloramphenicol was used for the detection of residues of the drug in biological samples. The extracted oil from fish was subjected to a rapid clean-up on a pre-packed silica gel cartridge prior to non-chromatographic tandem mass spectral analysis. Fat extracted from milk was analysed directly by on-line combined high-performance liquid chromatography/tandem mass spectrometry with rapid elution of chloramphenicol. Identification was on the basis of agreement of the daughter ion spectra obtained from sample extracts with that of the chloramphenicol standard. Detection was unambiguous at 0.5 mg kg-1. The sensitivity advantage normally expected with multiple reaction monitoring was not achieved owing to the effect of neutral noise phenomena.

Animals↗

Saturation of human chromosome 3 with unique sequence hybridization probes.

We have generated chromosome 3-specific recombinant libraries in both lambda and cosmid cloning vectors starting with somatic cell hybrids (hamster/human) containing either an intact chromosome 3 or a chromosome 3 with an interstitial deletion removing 75% of long-arm sequences. The libraries contained between 2 X 10(5) and 5 X 10(6) independent recombinants. Approximately 2% of the recombinants in these libraries contain inserts of human DNA. These were identified by hybridizing the recombinants to radioactively labeled total human DNA. Over 2500 recombinants containing human DNA were isolated from these various libraries and DNA was prepared from each of them. This represents 80,000 kb of cloned chromosome 3 sequences. One-third of the DNAs were digested with EcoRI or HindIII, and fragments free of repetitive sequences were radioactively labeled using random hexanucleotide primers and tested as unique sequence hybridization probes. Over 6500 of the fragments were tested and of these 758 were unique sequence probes with minimal or no background hybridization. Their hybridization only to chromosome 3 was verified. These probes, which were derived from 452 independent recombinants, should provide an effective saturation of human chromosome 3.

Animals↗

Effect of triphenylacrylonitrile derivatives on estradiol-receptor binding and on human breast cancer cell growth.

In a study of a series of 26 triphenylacrylonitrile derivatives (TPEs), we investigated the influence of several possibly interrelated factors on the proliferation of human breast cancer cell lines. (1) Chemical substituents: the test compounds were for the most part para-hydroxylated with increasingly bulky hydrophobic and/or basic side chains [isopropyloxy or (diethylamino)ethoxy] or standard reference compounds. (2) Relative binding affinities (RBAs): they competed diversely for [3H]estradiol (E2) binding to calf uterus cytosol and little, if at all, for binding to the [3H]tamoxifen-labeled antiestrogen binding site (AEBS) in lower speed supernatant. A multiparametric comparison of RBAs recorded for calf, rat, and mouse uterus cytosol estrogen receptor (ER) revealed a possible influence of species-specific receptor conformation and/or environment on binding. (3) Estrogen/antiestrogen potency: their stimulation and inhibition of the proliferation of the ER-positive human breast cancer cell line (MCF7) was measured. Compounds with only hydroxy substituents stimulated proliferation more markedly than methylated derivatives and had a maximum effect at 10(-11)-10(-6) M. Stimulation was related to the RBA for ER. Compounds with isopropyloxy or (diethylamino)ethoxy side chains only weakly stimulated MCF7 cell growth and more powerfully antagonized E2-promoted growth. The extent of inhibition depended upon the bulk of the side chain and could be reversed by 10(-7) M E2. Within the same concentration ranges, the test compounds were without effect on the BT20 ER-negative cell line. (4) Cytostatic and/or cytolytic activity: most compounds could arrest the proliferation of both MCF7 and BT20 cells at concentrations above 3 x 10(-6) M. This activity was thus independent of ER. Nevertheless, those compounds with a charged hydrophobic side chain, which were the most powerful antagonists of E2-promoted cell growth, were also the most cytotoxic. The overall results for all molecules on all parameters were submitted to a multivariate analysis (correspondence analysis) which revealed the progressive influence of increasing substitution by hydroxy and more bulky groups on the generation of antagonist activity and cytotoxicity.

Animals↗

Thoracic paravertebral block: a method of pain control.

The adverse effects of pain on acutely ill or traumatized patients are well documented. A variety of pain-relieving techniques are now available to meet the varied requirements for pain relief. This paper presents the results of a single, large-volume injection of bupivacaine 0.5% in the thoracic paravertebral space, achieving pain relief over several thoracic dermatomes in patients with respiratory compromise secondary to thoracic or upper abdominal injury. The block proved quick and simple to perform, with excellent clinical results of long duration and virtually no complications. Although not previously described, this single, large-volume injection approach to achieving an extensive thoracic paravertebral block may well become an important pain management technique in appropriate patients.

Abdominal Injuries↗