Intracardiac thrombus trapped in a patent foramen ovale

We describe a case of impending paradoxical embolism due to a thrombus trapped in a patent foramen ovale in a 22-year-old woman. Transthoracic and transesophageal echocardiography detected the thrombus. She was operated on and discharged asymptomatic.     

Revision ulnar neuroplasty

The most important factors in the evaluation and treatment of breast pain consist of a thorough history, physical, and radiologic evaluation. These can be used to reassure the patient that she does not have breast cancer. In the 15% of mastalgia patients who have life-altering pain and still request treatment, therapy may consist of a well-fitting bra, a decrease in dietary fat intake, and discontinuance of oral contraceptives or hormone replacement therapy. Those women still resistant to therapy may experience relief from evening primrose oil supplements, bromocriptine, tamoxifen, or GnRH analogues. Predicting which treatment will be most useful for any particular woman may be challenging. No differences in success rates were found to be associated with factors such as reproductive history, presenting complaint, personal or family history of breast disease, or subsequent need for breast surgery. The peak (but not basal) serum prolactin levels in response to thyrotropin releasing hormone stimulus has been predictive of success for hormonal treatment but is relatively invasive. A survey of treatments actually used was obtained from 276 consultant surgeons in Britain in 1990. Of those, 75% prescribed danazol. Others used analgesia (21%), diuretics (18%), local excision (18%), bromocriptine (15%), evening primrose oil (13%), tamoxifen (9%), a well-fitting bra (3%), and no treatment (10%). Breast specialists were more likely to begin treatment with primrose oil, tamoxifen, vitamin B6, and analgesia, reserving other hormonal therapies for more difficult cases. To further evaluate the women who have severe mastalgia but do not complete treatment regimens, a questionnaire was sent to 79 patients who failed to return to the Longmore Breast Unit of Western General Hospital, Edinburgh. Seventy-one women responded. Of these, 36 said they felt better, 19 said they felt no more could be done, 18 learned to live with it, 14 were not worried even if the pain recurred, 2 were pregnant, 10 were postmenopausal, and 5 were still taking the medications previously prescribed. The prognosis for women with breast pain is not always predictable. Women with cyclic breast pain often are relieved by events that alter their hormonal milieu, whereas noncyclic breast pain may last only 1 to 2 years. Sitruk-Ware and colleagues conducted a study of French women with fibroadenomas. They found an association between fibroadenomas and cyclic mastalgia occurring more than 1 year prior to the first full-term pregnancy. A retrospective, case-control study to determine if cyclic mastalgia was a risk factor for breast cancer was conducted on 210 newly diagnosed women with breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of dose, schedule, and route of administration on the in vivo toxicity and antitumor activity of two activated sulfhydryl derivatives of cyclophosphamide

Two cyclophosphamide (CP) derivatives, 4-S-(hexane-6-ol)-sulfidocyclophosphamide (C-1) and 4-S-(propionic acid)-sulfidocyclophosphamide (C-2), that hydrolyze spontaneously under physiological conditions to 4-hydroxycyclophosphamide, are compared to CP for antitumor activity in male C57BL/6 x DBA/2 F1 mice with ascites L1210 leukemia or solid Lewis lung carcinoma. When C-1 or C-2 is administered i.p. as a single injection at 10% lethal dose (approximately LD10) to mice bearing L1210 (1 x 10(5) cells i.p.), early treatment produces a 5- to 6-log tumor cell kill and results in substantial numbers of long-term survivors (greater than or equal to 30 days). Such antitumor activity is comparable to that of CP treatment. However, i.p. administration of either sulfido derivative produces liver atrophy and fibrosis of hepatic capsular structures. Hepatotoxicity is eliminated if single-dose C-2 (less than or equal to LD10) is administered i.v.; however, when administered by this route, C-2 results in only a 1-log cell kill of i.v. implanted leukemic cells as compared to the 4-log tumor cell kill obtained with CP given i.v. In addition to hepatotoxicity, C-2 causes an acute and dose-limiting toxicity in mice, manifested by severe muscular spasms and cessation of breathing. In the treatment of advanced L1210, C-2 shows no therapeutic advantage over CP. When mice bearing s.c. Lewis lung carcinoma receive early i.p. treatment with CP, C-1, or C-2, each drug results in long-term tumor-free survivors. However, CP (< LD10) consistently cures all mice, whereas C-1 or C-2 (approximately LD10) produces only 10 to 30% tumor-free survivors. These data suggest that, in the L1210 and Lewis lung tumor systems studied, the two activated CP derivatives offer no therapeutic advantage over CP. In addition, two forms of toxicity occur with these derivatives that do not occur with CP.     

Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara

The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses. Three distinct patterns of viral replication observed during and following primary viremia accounted for significant differences in survival times. High-level primary plasma viremia with subsequently increasing viremia was associated with rapid progression to AIDS (n = 2). A high-level primary plasma virus load with a transient decline and subsequent progressive increase in viremia in the post-acute phase of infection was associated with progression to AIDS within a year (n = 6). Low levels of primary plasma viremia followed by sustained restriction of virus replication were associated with maintenance of normal lymphocyte subsets and intact lymphoid architecture (n = 4), reminiscent of the profile observed in human immunodeficiency virus type 1-infected long-term nonprogressors. Three of four macaques that showed this pattern had been immunized with an SIV recombinant derived from the attenuated vaccinia virus, modified vaccinia virus Ankara. These data link the dynamics and extent of virus replication to disease course and suggest that sustained suppression of virus promotes long-term, asymptomatic survival of SIV-infected macaques. These findings also suggest that vaccine modulation of host immunity may have profound beneficial effects on the subsequent disease course, even if sterilizing immunity is not achieved.     

Neuropathic pain in rats is associated with altered nitric oxide synthase activity in neural tissue

Peripheral nerve injury may lead to a chronic neuropathic pain state that results from an increase in excitability of central neurons. This central sensitization is mediated via an N-methyl-D-aspartic acid (NMDA) receptor and may involve the production of nitric oxide (NO). As NO is suggested to play a role in nociceptive transmission following nerve injury, we examined for altered NO synthase activity at multiple levels of peripheral and spinal neural tissue in a rat model of neuropathic pain. Peripheral neuropathy was induced in rats (N = 12) by ligation of the left L5 and L6 nerve roots. Six other rats had sham surgery. An ipsilateral decrease in paw withdrawal threshold to mechanical stimuli confirmed the presence of a neuropathic pain state. Samples of the lumbar and thoracic spinal cords, L4, L5, and L6 dorsal root ganglia (DRGs), and the sciatic nerves were obtained from the lesioned and contralateral sides at 2 and 4 weeks after neuropathic surgery (N = 6 per group). In the lumbar spinal cord, a bilateral decrease in nitric oxide synthase (NOS) activity was observed 2 and 4 weeks after neuropathic surgery. NOS activity was increased in the ipsilateral L5 and 6 DRGs 2 weeks following neuropathic surgery. An increase in NOS activity in the DRG may be an early mechanism for inducing more central changes. The bilaterally decreased NOS activity in the lumbar spinal cord may be secondary to a negative feedback mechanism resulting from increased NO production in the spinal dorsal root ganglia. Multiple alterations in expression of NOS activity that occur in both peripheral and central processing may play a role in the pain behavior resulting from peripheral nerve injury. (Preliminary results of these studies have been presented in abstract form at the annual meetings of the Society for Neuroscience, 1994, and the American Society of Anesthesiologists, 1994).     

Parameters affecting the use of the lac repressor system in eukaryotic cells and transgenic animals

Elements of the lactose operon were used to study parameters affecting gene expression in cultured cells and transgenic animals. A Lac repressor protein containing a nuclear transport signal was shown to inhibit expression of a reporter gene by interacting with lac operator sequences. In cultured cells, operator sequence, operator placement and induction parameters were all shown to be important for obtaining tight repression of a reporter gene followed by high level expression upon induction. Induction levels were also dependent on the reporter gene, with the luciferase gene yielding higher induction levels than the chloramphenicol acetyltransferase gene. In transgenic animals, the lacI mRNA was not detected in the C57BL/6 mouse strain until the animal was exposed to a demethylating agent. After 5-azacytidine treatment, expression of lacI mRNA was detected in the brain, heart, kidney, lung and ovary. In the FVB transgenic mouse strain, expression of lacI mRNA was detected without 5-azacytidine treatment in the kidney, liver, lung, and testes. Preliminary experiments with double transgenic animals containing both lacI and operator/luciferase transgenes showed a decrease in luciferase expression compared to the luciferase-only animals in both tissue extracts and transgenic fetal primary cultures, although IPTG induction was not achieved in these animals or primary cultures. The applicability and challenges of the system for regulation of gene expression are discussed.