[Sensitivity in diathesis and affective psychoses. 1927].
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Biomedical subjects
Publications and source records attributed to M Nathan.
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A retrospective study was undertaken of all women attending a sexual health service during their pregnancies in the year 2000 in order to find the prevalence of sexually transmitted infections (STIs) and other conditions commonly screened for in sexual health services among this population. Data relating to demographics, sexual health screen and infections diagnosed were collected. All new female registrations during the same period were additionally identified. The prevalence of disease in the two groups was compared. Data on 164 patients who attended during their pregnancies in the year 2000 were analysed. One STI was identified in 59 patients (36%), two infections in nine patients (5%) and three infections in three patients (2%). An increased prevalence of STIs was noted in those aged 25 and under, compared with those over 25 (P < 0.001). Prevalence of STIs increased with gestation (0.01 < P > 0.05). Prevalence of STIs was higher in pregnant women (63/164; 38.4%) compared with all new female registrations (1094/5273; 20.7%; P < 0.001) during the same period. Additionally, 8.5% of pregnant women had a negative screen compared with 20% of all new female cases. This study shows the prevalence of STIs to be significantly higher among the pregnant women as compared with all women attending. A trend towards more frequent occurrence of an STI was seen with increasing gestation and young age. Prospective studies are needed to verify these results among an unselected population of pregnant women.
OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.
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Low-powered lasers were first used in the early 1980s to produce transventricular channels as an adjunct to coronary artery bypass graft surgery (CABG). Early results were encouraging, but because of the combined procedure, could not be attributed directly to use of the laser [1]. High-powered lasers were introduced into clinical practice in 1990 [2]. These lasers are powerful enough to create a transmyocardial channel with minimal thermal damage to surrounding tissues [3]. Clinical studies, using transmyocardial laser revascularization (TMR) as the sole operative therapy for patients with severe and diffuse coronary artery disease (CAD) who have Class III or IV angina, and are on medical therapy, have been conducted since 1993. Based on the results of these studies, the FDA granted approval for the use of TMR as a sole therapy. Clinical studies are currently underway to assess the results of combined TMR and CABG [4]. Results of four controlled randomized studies have been published [5-8]. The data from two of these studies formed the basis for FDA approval of two different types of laser systems. The results of these studies have not provided any additional insights into the mechanism of action of TMR, which remains the Achilles' heel of this procedure. In this review, background information about the TMR procedure will be discussed along with an analysis of the recently published randomized studies.
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Involvement of the inferior vena cava with tumor thrombus has been reported in 5 to 10% of patients with Wilms' tumor. Preoperative imaging usually alerts the surgeon to the extent of the intravascular extension. We present a case report of trauma to a previously undiagnosed Wilms' tumor that resulted in a fatal intraoperative pulmonary tumor embolus.
Transmyocardial laser revascularization (TMR) is a relatively new therapy for atherosclerotic coronary artery disease. Unlike well established surgical and percutaneous revascularization procedures, TMR is reserved for patients with advanced and severe forms of coronary artery disease that is unsuitable for other forms of revascularization. The results of TMR so far have been controversial with a bias toward steady and incremental adoption as sole therapy or in combination with coronary artery bypass graft surgery. The controversy surrounding TMR is related to the fact that its mechanism of action is not proven beyond a reasonable doubt. It is believed that angiogensis stimulation by the laser beam may be responsible for the relief of angina. However, the marked discrepancy in the symptomatic relief of angina and the increase in myocardial perfusion is not well understood. Other mechanisms proposed include direct perfusion through the laser channels, myocardial damage, denervation of ischemic myocardium and a placebo effect. It is possible that one or more of these mechanism may be responsible at various time intervals for the relief of angina. The challenge of TMR is related to improvement in perioperative outcomes, and long-term survival without worsening of left ventricular function. The achievement of these goals makes TMR an alternative therapy to what was formerly the only therapeutic option for these patients, namely: failed maximum medical therapy.
Following androgen ablation therapy, skeletal metastases from prostate cancer appear in some instances to show an increase in 99Tcm-methylene diphosphonate (99Tcm-MDP) uptake. Such a phenomenon could represent a mechanism to increase delivery of bone-seeking therapeutic agents to skeletal metastatic sites. The aim of this study was to characterize more precisely the potential increase in 99Tcm-MDP in skeletal metastases from prostate cancer following initiation of hormone therapy. Baseline bone scans were performed within 1 week of onset of hormone therapy in patients with stage D2 prostate cancer followed by multiple repeat bone scans for up to 4-6 weeks. The count density within metastatic lesions was divided by the average count density from several areas of normal bone to obtain a lesion to normal bone uptake ratio (L/N) for each lesion in each scan. Altogether, 61 skeletal metastases were identified on bone scans from five subjects. Eighty-four percent (51/61) of these lesions showed an increase in 99Tcm-MDP activity relative to normal bone following initiation of hormone therapy with a mean peak increase of 39%. Thirty-nine of these 51 metastatic lesions showed maximum uptake at 3 weeks post-onset of hormone treatment. From our findings, it appears that approximately 3 weeks following initiation of hormone blockade, most skeletal metastases from prostate cancer will demonstrate significantly enhanced 99Tcm uptake relative to normal bone. Consequently, it may be possible to improve the uptake and effectiveness of therapeutic bone-seeking radiopharmaceuticals by administering these agents following hormone therapy in patients with prostate cancer metastases.
The results presented in this paper are part of a current comparative study of genetic and environmental influences in three educational settings: Stockholm, Jerusalem and the Israeli kibbutz. We specifically wanted to investigate whether a more restrictive educational setting would decrease genetic influences. Here we report on comparisons of cognitive performance measures at several time points for twins/controls, boys/girls and within-pair similarity in MZ, DZ and controls. The tests used were the Raven Progressive Matrices, verbal, reading comprehension and arithmetic. The results show no differences between twins and controls, whilst gender differences seem to be smallest in the Stockholm sample and largest in Jerusalem. A pattern of genetic influences on cognitive performance was also clearly visible in Jerusalem. In Stockholm shared environmental influences at home and at school seemed even stronger than in the kibbutz. No consistent differences were found between tests or occasions.
Changes in spinal column height have been observed in response to different stress environments including vibration, gravity inversion, space flight, traction, and increased loading. Alterations in spinal height are dependent on body forces, externally applied forces, and properties of the discs and are considered relevant to understanding the normal and pathologic behavior of the spine. This study presents a sagittal plane, viscoelastic model of the spine that quantified the height change behavior of the human spine subjected to axial compressive forces similar to those experienced during quiet standing. The two-dimensional spine model was idealized as a collection of 23 rigid vertebral bodies and 23 deformable intervertebral discs. Time-dependent height losses were modeled using axial compressive creep material properties based on in vitro measurements obtained from the literature. The model demonstrated an instantaneous loss in height of 11.7 mm (0.67% of body height) and a height loss of 19.6 mm (1.1% of body height) at the end of 8 h. Changes in sagittal profile were estimated to contribute to 12% of the overall height loss after 8 hours. Discs in the lumbar region lost the most height, but the contribution of the lumbar region to the total height loss was 32%. The height loss contribution of the thoracic region was higher (57%), presumably because of the increased number of discs contributing to the total height loss in this region. For degenerated discs, the model predicted a similar instantaneous height loss but a 28% greater height loss after 8 h. These results suggest that the majority of spinal height loss is a direct result of intervertebral disc deformation and about two thirds of the total height loss occurs immediately on axial loading of the spine. Based on these findings, diurnal height changes in the spine are predicted to be much greater than previously believed.
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Reverse transcriptase (RT) is the key enzyme required for conversion of RNA to DNA. Cloning of Moloney murine leukemia virus (MMLV) RT has enable engineering an RT that lacks endogenous RNase H activity. RT catalyzes cDNA synthesis more efficiently in the absence of RNase H. We describe here a number of properties of MMLV RT and RNase H-minus MMLV RT not summarized in a single location elsewhere, providing a basis for best use of these enzymes in cDNA synthesis. In addition, general guidelines and detailed protocols are provided for use of MMLV RTs in one tube double-stranded cDNA synthesis, in [32P]cDNA synthesis, and in RT-PCR and long RT-PCR.
In the classic theory of airway lumen narrowing in asthma, active force in airway smooth muscle is presumed to be in static mechanical equilibrium with the external load against which the muscle has shortened. This theory is useful because it identifies the static equilibrium length toward which activated airway smooth muscle would tend if given enough time. The corresponding state toward which myosin-actin interactions would tend is called the latch state. But are the concepts of a static mechanical equilibrium and the latch state applicable in the setting of tidal loading, as occurs during breathing? To address this question, we have studied isolated, maximally contracted bovine tracheal smooth muscle subjected to tidal stretches imposed at 0.33 Hz. We measured the active force (F) and stiffness (E), which reflect numbers of actin-myosin interactions, and hysteresivity (eta) which reflects the rate of turnover of those interactions. When the amplitude of imposed tidal stretch (epsilon) was very small, 0.25% of muscle optimal length, the steady-state value of F approximated the isometric force, E was large, and eta was small. When epsilon was increased beyond 1%, however, F and E promptly decreased and eta promptly increased. The muscle could be maintained in these steady, dynamically determined contractile states for as long as the tidal stretches were sustained; when epsilon subsequently decreased back to 0.25%, F, E, and eta returned slowly toward their previous values. The provocative stretch amplitude required to cause active force or muscle stiffness to fall by half, or hysteresivity to double, was slightly greater than 2%. These observations are consistent with a direct effect of stretch upon bridge dynamics in which, with increasing tidal stretch amplitude, the number of actin-myosin interactions decreases and their rate of turnover increases. We conclude that the interactions of myosin with actin are at every instant tending toward those that would prevail in the isometric steady state, but tidal changes of muscle length cause an excess in the rate of detachment. These stretch-induced detachment events can come so fast compared with the rate of attachment that static equilibrium conditions are never attained. If so, then airway lumenal narrowing and the underlying contractile state would be governed by a dynamic mechanical process rather than by a mechanical equilibrium of static forces.
Picotamide is a dual thromboxane (Tx) A2 receptor antagonist/Tx synthase inhibitor although some observations suggest an anti-vasoconstrictor effect independent of TxA2 inhibition/antagonism. The aim of our study was to assess whether picotamide antagonises vascular contractions induced by different vasoactive substances in vitro. Picotamide inhibited competitively the contraction of rabbit aortic rings induced by the TxA2 mimetic U46619 (pA2 = 3.59) but also the contractions induced by phenylephrine (pA2 = 3.93) and serotonin (5-HT) (pA2 = 5.81) although in a not competitive way. Picotamide did not inhibit potassium-induced contractions, thus excluding aspecific effects on vascular smooth muscle. Picotamide inhibited 5-HT-induced platelet aggregation in vitro with an IC50 (212 microM) similar to that found when other aggregating stimuli are used, but it did not affect shape change (IC50 > 1 mM) suggesting that the effects of picotamide can not be ascribed to 5-HT2-receptor antagonism; in the same experimental conditions neither a Tx-receptor antagonist (BM13.177) nor a dual Tx-receptor antagonist/synthase inhibitor (ridogrel) affected 5-HT-induced platelet responses. Our studies demonstrate that picotamide exerts antivasoconstrictor and platelet inhibitory effects unrelated to TxA2 antagonism. This activity may contribute to the anti-thrombotic/anti-ischaemic effects of the drug in vivo.