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L Potter

Publications and source records attributed to L Potter.

At least 37 records · Page 2Linked to original sources

Global bioethics: converting sustainable development to global survival.

Millions of people in various parts of the world and within each country are presently surviving in categories described as "mere," "miserable," "idealistic," "irresponsible," and "acceptable." The term "acceptable survival" is proposed as a bioethical goal of global survival, looking beyond the 21st century to the year 3000 and beyond. The frequently used alternative term is "sustainable development," but in most contexts this is an economic concept and does not imply any moral or ethical constraints, except where these are spelled out. Acceptable survival, broadly defined, means acceptable to a universal sense of what is morally right and good and what will continue in the long term. The expanding dominant, but irresponsible, world culture is not an acceptable type of development because it cannot survive in the long term.

Bioethics↗

Fluoxetine efficacy in treatment resistant depression.

1. As many as 30% of depressed patients fail to respond to antidepressant drug therapy, and at least 60%-75% will not achieve complete recovery. Recently, several studies have suggested that newer, "second generation" antidepressants might be beneficial in treatment resistant depression (TRD). In the present study the authors examined the potential utility of fluoxetine in TRD by comparing its efficacy in patients with and without a prior history of antidepressant response. 2. 149 patients with MDD received fluoxetine 20mg daily for a minimum of 5 weeks: 43 (29%) had never responded to drug therapy (TRD patients), 41 (28%) did have a prior drug response (non-TRD patients) and 65 (44%) had never received any antidepressant treatment. Clinical response was defined as a > or = 50% reduction in baseline Hamilton Depression Rating score plus a final score < 7. 3. Compared to non-TRD patients, the TRD patients were more likely to have unipolar depression (p = 0.002), a chronic episode of > 2 years duration (p < 0.0001), a later age of illness onset (p < 0.0001), fewer prior episodes (p < 0.0001) and fewer prior drug treatments (p = 0.04). Overall, the response rate to fluoxetine was slightly greater in the non-TRD patients (76%) compared to the TRD patients (56%); however, this difference did not achieve statistical significance. 4. The present observations suggest that fluoxetine treatment of adequate duration may be beneficial for some patients with a prior history of refractory depression.

Adult↗

In situ correlation of synthesis and storage of parathormone in parathyroid gland disease.

The distribution and expression of parathyroid hormone (PTH) were investigated in normal and abnormal parathyroid tissue. PTH was detected using a monoclonal antibody with specificity for the 44-68 region of the PTH molecule. Prominent reactivity for PTH was seen in normal parathyroid with a granular pattern of staining. Active parathyroid tissue (adenoma and hyperplasia) showed much less reactivity for PTH, although there was prominent reactivity in the normal tissue around adenomas. Comparison of expression of PTH with that of parathormone mRNA showed a reciprocal pattern in normal tissue and, to a less marked extent, in abnormal tissue. Parathyroid carcinoma in particular had coinciding areas of PTH and PTH mRNA expression. Oxyphil cells had little or no PTH expression, except in the associated 'colloid' in some cases. The findings indicate an inverse relationship between storage and cellular synthesis of PTH, this being more marked in physiological than in pathological conditions of the parathyroid.

Adenoma↗

The acceptability of Norplant in Egypt.

Currently, the pill and IUD account for 83% of contraceptive use in Egypt; Norplant will be an important complement to those methods of family planning. In Egypt where childbearing begins early, and closely spaced pregnancies are the norm, the long duration of Norplant's effectiveness and its relative ease of use should be appealing. The Egyptian Fertility Care Society (EFCS) initiated a study in 1988 on the acceptability of Norplant in Egypt to study the clientele of the EFCS clinical trial in the five university teaching hospitals. The clinical trial participants were women in their thirties who had an average of four children. Most had used a method of family planning before Norplant, and were anxious to maintain contraceptive protection as most wanted no more children. Satisfaction with Norplant among users was high. In the survey, 93% of the women expressed satisfaction with the method. More than half (67%) of the women said they would consider using Norplant again in the future, and another 22% were undecided. Eighty-seven percent of the women who had not discontinued were planning to continue with their current Norplant set for the full five years. Egyptian women like Norplant because of its long duration of effectiveness, the site of insertion, its ease of use, and its relative lack of perceived side-effects compared to the pill and IUD. In Egypt where a reliable, long-term, but not permanent method of contraception is badly needed, Norplant should become a popular method of family planning.

Adult↗

Effect of partial obstruction of the rabbit urinary bladder on malate dehydrogenase and citrate synthase activity.

Previous studies have demonstrated that partial outlet obstruction in rabbits induced a significant decrease in oxidative metabolism in urinary bladder smooth muscle. The current experiments were designed to determine whether the decreased oxidative metabolism of obstructed bladder tissue is associated with alterations in the activities of specific mitochondrial enzymes. The activities of two important enzymes in the tricarboxylic acid cycle, malate dehydrogenase and citrate synthase, were measured in samples of bladder body and base from normal bladders and in bladders from rabbits in which partial outlet obstruction had been produced seven days prior to the experiments. The results can be summarized as follows: malate dehydrogenase activity was similar in bladder body and base isolated from control rabbits; and decreased by approximately 40% in both segments of the bladder isolated from obstructed rabbits. In contrast to malate dehydrogenase, citrate synthase activity was significantly higher in the bladder body than in the base of normal rabbits. Outlet obstruction caused about a 50% decrease in activity of this enzyme in the bladder body, but had no significant effect on citrate synthase activity of the bladder base. These findings demonstrate that the deficiency in bladder function following partial outlet obstruction is associated with a marked decrease in the activities of two essential enzymes in oxidative metabolism: malate dehydrogenase and citrate synthase. This decrease in enzyme activity is consistent with the previously observed decrease in oxidative metabolism and would be expected to lead to an inability of the tissue to supply sufficient metabolic energy for proper contractile function.

Animals↗

In situ hybridization of immunoglobulin light chain mRNA in paraffin sections using biotinylated or hapten-labelled oligonucleotide probes.

An in situ hybridization technique has been developed for the detection of immunoglobulin light chain mRNA in routine pathology specimens. The method detects kappa or lambda constant region sequences using a cocktail of synthetic oligonucleotide probes labelled with biotin or fluorescein 5-isothiocyanate (FITC) reporter molecules. The probes were labelled at flanking sites chemically by primary amine directed acylation and by 'homopolymer tailing' with terminal deoxynucleotidyl transferase using non-radioactive nucleotide analogues. The mRNA was unmasked in the formalin-fixed tissue sections by digestion with varying concentrations of proteinase K, and the hybrids were demonstrated using alkaline phosphatase with either a streptavidin/biotin based four-stage system or an anti-FITC antibody based detection system. Alkaline phosphatase was visualized using a Fast Red naphthol-capture method and the sections were counterstained with haematoxylin. The results confirm that the method is specific for kappa or lambda mRNA and show that specific mRNAs can be detected in routine formalin-fixed sections using non-radioactive techniques with retention of good morphology. The method reliably detects light chain mRNA in cells expressing secretory immunoglobulin. The protocol can also be applied to tissue rich in endogenous biotin by using hapten-labelled probes.

Biotin↗

Ontogeny of bladder function in the rabbit.

Although numerous experimental studies have addressed urinary bladder innervation, physiology and pharmacology, little information is available concerning the ontogeny of bladder function. The present study describes the developmental aspects of bladder mass, bladder capacity, pressure development and emptying in white New Zealand rabbits one day of age through maturity (11 to 15 weeks of age). The following studies were performed: Cystometry, pressure generation, rate of pressure generation, and emptying responses to field stimulation, cholinergic and purinergic stimulation using the in vitro whole bladder model. The results of these studies can be summarized as follows: 1) body weight and bladder weight increased in proportion to each other, bladder capacity increase proportionally with development until eight weeks of age, then increased substantially greater than body and bladder weight between eight and 11 to 15 weeks of age; 2) the ability to empty is similar for all ages; 3) pressure responsiveness to field stimulation, bethanechol, and ATP is greater at one day? of age, intermediate at one week of age, and similar for the other age groups; 4) The response to ATP (purinergic transmitter) is of an equal magnitude to the cholinergic response at one day, and reduces rapidly to approximately 45% of the cholinergic response by four weeks. Desensitization of the bladders to ATP reduced the response to field stimulation in the one day bladders to a significantly greater degree than the other age groups. These functional results indicate a marked alteration in cholinergic and purinergic response between the one day and the four week old rabbit bladders, with the response of the one week old bladders in between. The responses of the four, eight, and 11 to 15 week bladders was similar for equal volumes even though the bladder mass increased over threefold. This indicates that the ability of the bladder to generate pressure (during development) is not directly related to bladder mass.

Adenosine Triphosphate↗

Reduced rate of recurrent genital herpes infections with lithium carbonate.

Preliminary observations indicate that lithium carbonate may have an anti-herpes simplex virus activity. We conducted a randomized, double-blind, placebo-controlled trial of oral lithium therapy in 10 healthy women with chronic, recurrent genital herpes infections. During one year of lithium treatment at a mean (+/- SD) daily dose of 587 +/- 49 mg and an average plasma lithium level of 0.51 mEq/L, we observed a significant reduction in the total monthly duration of all herpes episodes (p less than .01), the average duration of each herpes infection (p less than .01), the maximum symptom severity (p less than .01), and a clinical severity index score (p less than .004). The onset of prophylaxis was gradual, with the duration of each episode declining by an average of 0.5 days per month. The present data indicate that chronic lithium therapy may be effective in preventing recurrent genital herpes infections.

Adolescent↗

Rapid identification of donor and recipient cells after allogeneic bone marrow transplantation using specific genetic markers.

The fate of the donor graft in allogeneic bone marrow transplantation, the presence of chimaerism and early relapse can be monitored by identification of the donor or recipient origin of haemopoietic cells in peripheral blood and bone marrow. We have done this by the use of highly informative locus-specific hypervariable DNA probes in two sex and blood group matched transplants. In four sex mismatched transplants the Y chromosome was identified by in situ hybridization using a biotinylated Y probe. Early engraftment by day 13 was detected in five of the six patients. Transient chimaerism occurred in half of the cases and was accompanied by the temporary appearance of the Philadelphia chromosome in one patient with chronic myeloid leukaemia without subsequent relapse. Persistence of the graft in the face of falling peripheral counts was documented in four of the six patients studied. The morphology as well as origin of the haemopoietic cells could be characterized by the Y probe analysis. In one patient, recipient lymphocytes were shown to co-exist with myeloid series of donor origin. We conclude that both techniques are highly specific, sensitive and can provide information within 24-48 h. Thus they are of value in guiding early therapeutic intervention in allogeneic transplantation.

Blotting, Southern↗

Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder.

This study evaluated the clinical efficacy and safety of a new triazolobenzodiazepine, adinazolam, and imipramine in 40 patients with carefully diagnosed major depressive disorder. Overall, adinazolam was found to be as effective as imipramine. In addition, when patients with more severe, melancholic, subtype of depression were examined, adinazolam was also as effective as imipramine. With the exception of sedation, adinazolam patients demonstrated fewer overall adverse events than imipramine subjects. These results suggest that adinazolam may represent an interesting antidepressant compound.

Adolescent↗

Effect of carbamazepine on psychomotor performance in näive subjects.

The effect of a single dose of carbamazepine (CBZ), 10 mg kg-1, on a battery of simple psychomotor tests was investigated in 12 healthy subjects (6 male, 6 female) in a balanced randomised double blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free plasma CBZ, and CBZ 10, 11 epoxide concentration were performed at 10, 12, 14, 16, 18 and 34 h after oral dosing (23.00 h the previous evening). CBZ impaired i) critical flicker fusion threshold frequency at all time points up to 18 h (p less than 0.005); ii) total choice reaction time at 10 h (p less than 0.005) and 18 h (p less than 0.008); iii) card sorting at 14 h (p less than 0.001). No significant effect on finger tapping was noted. Subjects adjudged themselves more sedated on CBZ as compared to placebo at 12, 14 and 16 h (p less than 0.008). Plasma total and free CBZ concentrations (mean +/- SD) peaked at 10 h (8.8 +/- 0.2 mg 1-1) and 16 h (1.88 +/- 0.3 mg 1-1) after dosing respectively. CBZ 10, 11 epoxide values were all less than 10% of total CBZ concentrations and, therefore, were unlikely to contribute to the pharmacodynamic effect. Total choice reaction time was significantly more impaired in females (p less than 0.05) but no sex difference occurred with the other tests or CBZ concentrations at any time point. No significant correlations were found between individual total or free CBZ concentrations and corresponding test performances at each time point.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Possible nonlinear pharmacokinetics of desipramine after once daily dosing.

Desipramine (DMI) plasma concentrations were measured in depressed outpatients treated with desipramine hydrochloride. Plasma level determinations were measured 24 hours after a single dose of DMI 50 mg, and then at weekly intervals thereafter while receiving once daily bedtime dosing with DMI 150 mg or 200 mg. The 24 hour DMI concentration was significantly, and rather closely correlated with steady state DMI levels (r = 0.74, p less than .001) (prediction coefficient [r2] = 55%). However, steady state plasma levels of DMI were higher than would be predicted based upon prior studies which also examined the relationship between steady state and 24 hour desipramine plasma concentrations. We speculate that the single bedtime administration of DMI in the present study may have led to saturation of metabolic hepatic enzymes during the first pass of the drug through the liver. The possibility of nonlinear DMI pharmacokinetics may be of clinical importance to some patients receiving a single, daily, high dose of medication.

Adult↗

Desipramine and 2-hydroxydesipramine plasma levels in endogenous depressed patients. Lack of correlation with therapeutic response.

Studies of the relationship between plasma concentrations of desipramine hydrochloride and clinical response have shown contradictory results, and only one prior study examined 2-hydroxydesipramine and its relationship to treatment. We therefore performed a study in a large, carefully diagnosed group of depressed patients taking fixed maintenance doses of desipramine to elucidate a potential relationship between clinical response and plasma concentrations of desipramine and 2-hydroxydesipramine. There was no significant correlation between clinical response and steady-state plasma levels of desipramine, 2-hydroxydesipramine, or the sum of desipramine plus 2-hydroxydesipramine. Although some commercial laboratories suggest a specific therapeutic plasma level "range" for desipramine, our data provide no support for such a range, nor for the routine measurement of plasma desipramine and 2-hydroxydesipramine concentrations in depressed patients.

Adolescent↗

Cimetidine-induced alterations in desipramine plasma concentrations.

Concurrent administration of cimetidine for 4 days to eight patients taking maintenance doses of desipramine led to significant elevations of desipramine (P less than 0.001) and its hydroxylated metabolite 2-hydroxydesipramine (P less than 0.001). The mean increase in desipramine plasma levels was 51% and that for 2-hydroxydesipramine was 46%. The present results suggest that tricyclic antidepressant plasma level monitoring might be indicated for certain patients taking concurrent cimetidine and desipramine.

Adult↗

Relationship between tricyclic antidepressant plasma levels and clinical response in patients treated with desipramine or doxepin.

A study examining the relationship between plasma levels of tricyclic antidepressants (TCA), clinical response, and side effects was performed in patients with major affective disorder. Patients received either desmethylimipramine (DMI) (150-200 mg/day) or doxepin (200 mg/day) for 4 weeks. No significant correlations were found between plasma levels and either clinical response or side effects when males and females were analyzed together. A significant correlation between plasma levels and response was found in females taking desmethylimipramine. Support for the finding that females may show a stronger relationship than males between clinical response and plasma TCA levels is provided from analysis of previous studies in the literature.

Adult↗

Double-blind comparison of doxepin and desipramine in patients with primary affective disorder.

A double-blind comparison of doxepin versus desipramine was performed in carefully defined patients with research diagnosis of Primary Affective Disorder. While both drugs showed equal efficacy after 4 weeks, doxepin demonstrated a more rapid onset of action and surprisingly few side effects. Desipramine did not prove to be "activating" and did not worsen agitated depression. Although doxepin showed few autonomic side effects, it was nevertheless sedating, indicating that tricyclics with more anticholinergic effects are not necessarily more sedating drugs.

Adult↗