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Biomedical subjects

J Welch

Publications and source records attributed to J Welch.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effects of minor groove binding drugs on the interaction of TATA box binding protein and TFIIA with DNA.

TBP (TATA box binding protein), a general transcription factor required for proper initiation of gene expression by RNA polymerase II, and minor groove binding drugs (MGBs) both interact with DNA within the minor groove at AT sites. This study has evaluated MGBs as inhibitors of DNA/TBP complex formation by gel mobility shift assays. Our results demonstrate that reversible MGBs (DAPI, distamycin A, Hoechst 33258, and netropsin) are effective inhibitors of the formation of DNA/TBP complex and that distamycin A is the most potent (0.16 microM inhibits TBP complex formation by 50%). CC-1065, a drug that covalently binds to DNA in the minor groove, is even more active than distamycin A (0.00085 microM inhibits TBP complex formation by 50%). Significantly more CC-1065 (0.009 microM) is required to break up preformed DNA/TBP complex compared to the drug concentration needed to prevent complex formation. In comparison, the order of drug addition has little influence on the ability of reversible MGBs to disrupt DNA/TBP complex. In the presence of TFIIA, a factor that enhances TBP association with DNA, greater drug concentrations (distamycin A and CC-1065, respectively) are needed to disrupt a preformed complex of DNA/TBP/TFIIA. In comparison to MGBs, drugs capable of binding to DNA by intercalation are generally weaker at blocking TBP complex formation except for hedamycin, which can intercalate and irreversibly bind to DNA and is as effective as reversible MGBs.

Base Sequence↗
PubMed1994

Setting up regional audit in genitourinary medicine and HIV: the south east Thames experience.

Audit at regional level is a useful complement to local audit, especially in small specialties. Regional audit can reduce professional isolation and lead to the development of uniformly high standards in the care given by a variety of providers. The development of regional audit in genitourinary medicine in South East Thames (UK), and of HIV medicine in South Thames, is described. Meetings are held quarterly, and concentrate on standard setting and development of guidelines. Information about the practice of individual units is collected by questionnaire, the results presented, and guidelines developed. Participation in completing questionnaires and attending the meetings is good. Regional guidelines in eleven topics have been produced, and methods of auditing changes in practice are now being assessed. A regional common data-set is being developed to assist in the audit process.

Ambulatory Care↗
PubMed1994

Clozapine-induced seizures and EEG changes.

Clozapine, an atypical antipsychotic drug, is widely used in refractory schizophrenia. At New Hampshire Hospital, 7 of the first 35 patients treated (20%) had convulsions. Patterns were tonic-clonic (5), complex partial (2), and myoclonic (3). Seizures were dose-related and may be anticholinergic in etiology. EEG changes are frequent with clozapine, particularly as dosage is increased. Twenty-six of 35 patients (74%) had EEG abnormalities at some time during clozapine treatment. EEG is a sensitive means of detecting clinical toxicity. When EEG abnormalities (slowing, dysrhythmia, or paroxysmal discharges) are detected, immediately lowering the dose by at least 25-50 mg per day and adjusting weekly until EEG returns to baseline can reduce the incidence of seizures.

Adult↗
PubMed1993

Moving beyond the Patient Self-Determination Act: educating patients to be autonomous.

This article explores the limitations of the Patient Self-Determination Act. We need to think of advance directives as a process of understanding, reflecting, and discussing, not just a written document. Further, health care professionals must initiate the process of advance directive education in the outpatient setting. Our dialysis unit has successfully integrated this view into daily care of patients and families.

Advance Directives↗
PubMed1992

Neglect and visual recognition.

B.Q., a right-handed woman who had suffered a stroke affecting the right parietal region, showed visuospatial neglect and problems in recognizing seen objects and faces. Investigation of her visual recognition problems revealed a striking inability to identify the left sides of chimaeric objects and faces. Often, B.Q. would deny that the stimulus was chimaeric at all, and she was remarkably poor (though above chance) at discriminating chimaeric from normal faces. Even when left-sided details had been accurately traced or described, they were often either ignored in reporting the identities of the constituent parts of a chimaeric or assimilated in some way to the information from the right side. Neglect of the left side was more pronounced for chimaerics which approximated an individual face or object. It occurred regardless of the chimaeric's position in B.Q.'s field of vision, and was found with brief (200 ms) presentations of stimuli confined to her (perimetrically intact) right visual field. When chimaeric faces were inverted, B.Q. continued to neglect the side of the chimaeric falling to her left, which implies that the neglect did not operate in entirely object-centered coordinates. However, left-sided information could be used if it was critical in determining the identity of an object or a face. We suggest that this could explain B.Q.'s lack of neglect of individual words, for which left-sided (initial) letters are often crucial to successful recognition. An account of her deficit is proposed, involving an interaction between moderately defective pick-up of left-sided information in an object-based coding system and preserved access to stored representations of familiar visual stimuli.

Attention↗
PubMed1991

Inflammatory pseudotumors of the spleen.

Inflammatory pseudotumors are uncommon benign lesions that have been found in numerous organ systems. However, their appearance within the spleen is decidedly rare. Grossly, pseudotumors appear as well-circumscribed, encapsulated masses, while microscopic examination reveals a polymorphous inflammatory cell infiltrate occurring variably with granulomatous reaction, fibrosis, and cell necrosis. Because they often present either as unexplained, asymptomatic masses or with vague constitutional symptoms, splenic inflammatory pseudotumors can raise suspicion for a primary splenic neoplasm, such as lymphoma. Splenectomy is the treatment of choice.

Female↗
PubMed1991

Disentangling neglect and hemianopia.

In this paper we report findings which question the diagnosis of a hemianopia in B.Q., a 66-year-old lady who shows unilateral spatial neglect following a lesion to the right parietal lobe. The presence of a hemianopia has been indicated following two independent assessments of B.Q.'s visual fields. We examined B.Q.'s performance on a visuo-spatial task in which single or double stimuli were displayed left and right of a central fixation point. B.Q. failed to report left stimuli when the fixation point was continuously displayed (OVERLAP CONDITION). This performance is consistent with the suggestion of a left hemianopia as indicated by perimetric field testing. In a further condition the fixation point was extinguished prior to stimuli onset (GAP CONDITION). B.Q. consistently responded to left stimuli in the gap condition and also showed improved performance to right stimuli. Eye movements were recorded on a separate testing session, in which B.Q. showed a normal saccadic response to left targets in the gap condition, but not during the overlap condition. These results suggest that B.Q.'s failure to report left stimuli during field plotting is due to her neglecting left stimuli and not because she has a visual field defect. By using a testing procedure which reduces the severity of neglect B.Q. is able to respond to left stimuli. Reducing the severity of B.Q.'s neglect also abolishes the apparent hemianopia. Standard field plotting techniques which use a consistently displayed fixation point may not be appropriate for the testing of neglect patients' visual fields.

Aged↗
PubMed1991

Head circumference and intellectual performance of patients with Duchenne muscular dystrophy.

The head circumferences of 64 patients with Duchenne muscular dystrophy were measured and found to be greater than those of a normal population. The patients had relative, and in 12 cases, absolute macrocephaly. 47 of the 64 patients underwent intelligence testing and were found to be significantly intellectually impaired, particularly in verbal and language skills. There was no correlation between head circumference or absolute macrocephaly and intellectual performance. The cause of macrocephaly in these patients is unknown and its relevance to the aetiology of intellectual impairment in Duchenne muscular dystrophy is not yet clear.

Adolescent↗
PubMed1991

Stress- and endotoxin-induced increases in brain tryptophan and serotonin metabolism depend on sympathetic nervous system activity.

Stressful treatments and immune challenges have been shown previously to elevate brain concentrations of tryptophan. The role of the autonomic nervous system in this neurochemical change was investigated using pharmacological treatments that inhibit autonomic effects. Pretreatment with the ganglionic blocker chlorisondamine did not alter the normal increases in catecholamine metabolites, but prevented the increase in brain tryptophan normally observed after footshock or restraint, except when the duration of the footshock period was extended to 60 min. The footshock- and restraint-related increases in 5-hydroxyindoleacetic acid (5-HIAA) were also prevented by chlorisondamine. The increases in brain tryptophan caused by intraperitoneal injection of endotoxin or interleukin-1 (IL-1) were also prevented by chlorisondamine pretreatment. The footshock-induced increases in brain tryptophan and 5-HIAA were attenuated by the beta-adrenergic antagonist propranolol but not by the alpha-adrenergic antagonist phenoxybenzamine or the muscarinic cholinergic antagonist atropine. Thus the autonomic nervous system appears to be involved in the stress-related changes in brain tryptophan, and this effect is due to the sympathetic rather than the parasympathetic limb of the system. Moreover, the main effect of the sympathetic nervous system is exerted on beta- as opposed to alpha-adrenergic receptors. We conclude that activation of the sympathetic nervous system is responsible for the stress-related increases in brain tryptophan, probably by enabling increased brain tryptophan uptake. Endotoxin and IL-1 also elevate brain tryptophan, presumably by a similar mechanism. The increase in brain tryptophan appears to be necessary to sustain the increased serotonin catabolism to 5-HIAA that occurs in stressed animals, and which may reflect increased serotonin release.

Animals↗
PubMed1990

Electron microscopic detection of human parvovirus (B19) in a patient with HIV infection.

We report the findings on an HIV-positive patient found to be infected with human parvovirus B19. In a comparative study of sequential sera, direct electron microscopy (EM) had the same sensitivity as DNA hydridization for the detection of the virus. EM did not require specific reagents and also yielded information on the state of the virus; i.e., whether random or complexed, and the type of antibody involved. The presence of parvovirus complicated the judgement as to drug treatment. This case also highlighted the importance of diagnosing the presence of opportunistic viral infections that have no, or low-grade, pathogenic activity.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The distance to the stomach for feeding tube placement in children predicted from regression on height.

Nurses use several external measures referenced to the head and chest to gauge the insertion distance for orogastric and nasogastric (NG) tubes. Few of the measures have been tested. However, in previous studies height was the external measure most correlated with esophageal length both in children and adults. In this study, the ability of previously published regression equations on height to predict esophageal length for NG-tube insertion in 107 children was evaluated. The regression equations were examined for stability, predictive performance, and the likely positions of the tube. The data were heights and esophageal lengths obtained from esophageal manometry records and hospital charts. The predicted values for nasal insertions were biased and averaged 2.4 cm too long (R2prediction = .56, n = 30). Prediction errors greater than 5 cm in absolute value occurred in 25% of the nasally-referenced sample. The predicted values represented overestimates in 18 nasally referenced cases that were 11.5% longer on the average than the measured esophageal lengths. In contrast, the predicted values for the oral insertions were unbiased (R2prediction = .92, n = 77), and gave accurate predictions in the majority of cases. Eighty percent of the oral predictions were within +/- 1.5 cm of the measured esophageal length and represented percentage errors between 0 and 7% (M = 3%, n = 50).

Adolescent↗