Alteration of Human Placental Vascular Tone by Antiarrhythmic Medications In Vitro

Antiarrhythmic and Placental Vessels. Introduction : Antiarrhythmic medications are commonly used during pregnancy for treatment of maternal or fetal arrhythmias, but little is known about their effect on human placental vascular tone and, consequently, placental blood flow. The objective of this study was to evaluate the tone responses caused by antiarrhythmic medications in human placental vessels from normal term pregnancies in vitro.
Methods and Results : Isolated human placental arteries and veins from uncomplicated term pregnancies incubated in Krebs'-bicarbonate under 5% oxygen/5% carbon dioxide/balance nitrogen (PO₂ 35 to 38 torr) were exposed to cumulative doses of quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, digoxin, and adenosine after submaximal contraction with 5-hydroxytryptamine. The study was conducted both in the presence and absence of endothelium. The addition of the tested medications caused a significant, dose-dependent relaxation of human placental arteries and veins except for adenosine, which induced a sustained, dose-dependent contraction of human placental vessels regardless of the presence or absence of tone. Removal of the endothelium did not alter these responses.
Conclusions : Based on these results, the medications tested should have no decremental effect on placental blood flow, with the possible exception of adenosine, which causes significant. dosedependent contraction of human placental vessels in vitro. Should similar contraction be present in vivo, it may have an adverse effect on the fetus when administering adenosine to pregnant women at term or during labor.     

Intrauterine Growth Retardation of Unknown Etiology. I. Serum Complement and Circulating Immune Complexes in Mothers and Infants

ABSTRACT: Complement (C) and circulating immune complexes (CIC) levels were measured in 22 full-term pregnant women and 15 of their small-for-gestational-age (SGA) offspring in order to seek evidence supporting an immunological etiology for placental lesions related to idiopathic intrauterine growth retardation. We used 19 normal full-term pregnant women and 18 of their infants with birthweight above the 25th centile of the ponderal curve as a control population for this study. C levels were significantly lower in mothers of SGA infants than in controls (146.6 ± 46.6 and 183.6 ± 36.6 respectively, p < 0.01). CIC were present in the sera of 5 out of 22 mothers of the SGA group and in 3 out of the 15 infants sera. No CIC were found in the sera of mothers or infants from the control group. Placental lesions were observed in 14 out of the 22 (64%) cases studied in the SGA group and in 1 of 11 (9%) of the controls. Two placentas from SGA infants showed acute atherosis, and deposits of IgM and C₃ were found in their vessel walls. These data are in favor of an immunological mechanism for intrauterine growth retardation of unknown etiology.     

IMMUNOCYTOCHEMICAL EXPRESSION OF THE 70 kD HEAT SHOCK PROTEIN IN ISCHAEMIC BOWEL DISEASE

Heat shock proteins (HSPs) are a family of polypeptides which are induced in response to diverse forms of cell injury including hyperthermia, anoxia, ethanol, heavy metals, and others, with a presumably protective function. Among several species of HSPs, the 70 kD protein (HSP70) is the most abundant and consistently induced in mammalian cells. Anti-HSP70 monoclonal antibody and a standard immunocytochemical method were used to study the expression of HSP70 in 28 surgical specimens of small and large intestines from patients with ischaemic bowel disease. Strong immunoreactivity was observed in viable, regenerating cells of both the crypt and surface epithelium within or adjacent to the necrotic foci in 86 per cent of the ischaemic bowel specimens. Staining was mostly cytoplasmic, but focally both cytoplasmic and nuclear. Smooth muscle cells of the muscularis mucosae in the ischaemic areas of some cases also showed immunoreactivity. On the other hand, HSP70 was not expressed in control specimens of small and large intestine or in colonic specimens of Crohn's disease, ulcerative colitis, and adenocarcinoma. These findings suggest a possible role of HSP70 in intestinal epithelial and smooth muscle cell response to ischaemic injury, especially in the recovery phase.     

Prosthodontic decision‐making: what unprompted information do dentists seek before prescribing treatment?

Summary  This study explored the nature of the unprompted information that clinicians seek before making a treatment decision and whether this decision corresponded with the clinical parameters of the case. Interns, general practitioners (GP) and prosthodontists ( n  = 70, mean age 33 years, range 23–68) were presented with a written vignette of partial edentulism that included two spaces and were invited to ask any questions for the purpose of making a treatment recommendation. A list of 48 potential question/answer items was available to the interviewer, of which 38 were asked. These were then allotted to four thematic categories. Mean number of questions asked did not differ significantly amongst groups, although prosthodontists asked significantly more questions in the 'clinical and radiographic information' category than GPs ( P  = 0·0001) and interns ( P  = 0·003). The relationship between a prescribed treatment and questions asked was tested by dichotomizing all recommendations into 'possible' or 'not possible' based on the authors' knowledge of the actual case history. There were no significant differences amongst the groups in the frequency of prescribing 'possible' treatment (Pearson chi-square 0·083 and 0·108 for upper and lower spaces, respectively), but those who prescribed 'possible' treatment asked significantly more questions in the 'clinical and radiographic information' category, specifically about bone adequacy in the edentulous areas: upper jaw ( P  = 0·0001) and lower jaw ( P  = 0·003). It may be concluded that prosthodontists generally opted for more 'possible' treatments, as well as seeking items of information that seemed to improve the chance of making recommendations that conformed to the actual case characteristics.     

Long-Term Pacing in Heart Transplant Recipients is Usually Unnecessary

The indications for and timing of permanent pacing were reviewed in all 17 of 154 adult heart transplant recipients at this center who have had permanent pacemakers implanted. Resting 12-lead ECGs recorded during routine follow-up were examined. A prospective study of pacing requirement was then undertaken. Holter monitoring was performed before and after reprogramming the pacemakers to VVI mode at 50 beats/min. Exercise responses in various pacing modes were then assessed in seven patients with rate responsive pacemakers using a standard Bruce protocol treadmill test. The indication for pacing was sinus node dysfunction in 59% (10/17) and atrioventricular (AV) block in 41% (7/17). The majority of pacemakers were implanted between seven and 21 days after transplantation. There was a progressive reduction in the frequency of pacing on 12-Jead ECGs with time after transplantation. Eight of 14 patients with empirically selected programming paced during Holter monitoring. After reprogramming to 50 beats/ min VVI mode only three of 14 patients, all with sinus node dysfunction, paced. Rate responsive pacing made no difference to exercise time. The requirement for long-term pacing in cardiac transplant recipients is small (3/154) and is limited lo patients with sinus node dysfunction. Rate responsive pacing did not increase exercise tolerance.     

Prazosin-induced Blockade of Extraneuronal Uptake Facilitates Dopaminergic Modulation of Muscle Twitches in Rat Vas Deferens

Preliminary findings in our laboratory have shown that prazosin augmented the inhibitory effects of dopamine on the electrically-evoked muscle twitches in rat vas deferens. In this study, we opted to investigate the underlying mechanism and whether a prazosin-induced blockade of extraneuronal uptake process may be involved. Cumulative additions of dopamine (1.8 times 10^?7-4.4 times 10^?5m) elicited slight (<30%) but dose-related inhibition of electrically-evoked (0.05 Hz, 1 ms duration and supramaximal voltage) muscle twitches of the vas deferens. Pretreatment with cocaine (10 μm), prazosin (50 nm) or oestradiol (10 μm) produced comparable potentiation of the inhibitory responses of dopamine; the pD₂ values to dopamine amounted to 4.47 ± 0.20, 4.72 ± 0.21 and 4.56 ± 0.19, respectively. A lower concentration of prazosin (5 nm) failed to alter dopaminergic responses. Further potentiation of dopamine responses was demonstrated in tissues preincubated with a combination of cocaine plus prazosin (50 nm), or cocaine plus oestradiol (pD₂, 5.40 ± 0.11 and 5.42 . 0.05, respectively). However, a mixture of all three drugs failed to elicit any further increase in dopamine responses, a finding that may suggest an extraneuronal uptake blocking activity for prazosin. Inhibition of muscle twitches evoked by bromocriptine, a dopaminoceptor agonist which is not a substrate for extraneuronal uptake, was not affected by prazosin (50 nm) pretreatment. The findings presented in this study emphasize the role of dopamine in modulating noradrenergic neurotransmission in rat vas deferens. More importantly, the results suggest that prazosin may act to block the extraneuronal uptake at noradrenergic sites, an effect that may account for its capability to facilitate dopaminergic modulation of noradrenergic neurotransmission.     

Malignancy: Meningeal Myeloma: A Case Report and Review of Literature

Purpose: Report and review of an uncommon complication of multiple myeloma. Methods: We report a case of leptomeningeal myeloma and using Medline, review previously reported cases. Results: We found 35 previously reported cases of meningeal myeloma. Of the 36 cases, including the present case, the male to female ratio was 2:1 with a median age of 58 years (range, 31 to 83 years). Forty five percent of the patients had circulating plasma cells and 90.9% had plasma cells in the cerebrospinal fluid. All but 4 cases were diagnosed antemortem. Thirty patients had a pre-existing diagnosis of multiple myeloma, while leptomeningeal disease was the presenting feature in six. Management included a combination of intrathecal chemotherapy and radiation therapy, radiation therapy alone or intrathecal chemotherapy alone in 14, 3, and 3 patients respectively. Thirteen patients also received systemic chemotherapy in addition to some form of local therapy. The median survival for the entire group was 8 weeks (range 4 days to 18 months). Even those who initially responded to local therapy relapsed in the central nervous system (CNS) or succumbed to systemic disease. Five of six patients in whom CNS disease was the presenting feature survived 4 weeks or less. Conclusions: Leptomeningeal involvement is a rare and fatal complication of multiple myeloma with a short survival despite aggressive intrathecal and systemic chemotherapy and radiation therapy.