Flucytosine monotherapy for cryptococcosis

Medullary carcinoma is a recently recognized tumor of the kidney with distinctive microscopic features; the most notable are diffuse and glandular growth patterns, inflammatory infiltrates, and rhabdoid/plasmacytoid cells. It is a clinically aggressive tumor that occurs in relatively young patients. Moreover, this tumor shows a peculiar clinical association: it occurs in patients with sickle cell hemoglobinopathy. The case presented is that of a 37-year-old black woman with a history of bronchial asthma who died suddenly. Autopsy showed a 4-cm renal mass with extension to the inferior vena cava and metastases to the liver. Histologic evaluation showed the characteristic findings of medullary carcinoma of the kidney. This diagnosis prompted the investigation and subsequent detection of sickle cell trait in the deceased, alerting the family to the genetic nature of her illness. This case is the first report of this entity since the original described series of patients and shows the unique nature of this cancer as a marker of a genetic medical disease.     

Selective convective brain cooling during normothermic cardiopulmonary bypass in dogs

BACKGROUND: Neurologic complications, primarily resulting from ischemic insults, represent the leading cause of morbidity and disability, and the second most common source of death, after cardiac operations. Previous studies have reported that increases (as occur during the rewarming phase of cardiopulmonary bypass [CPB]) or decreases in brain temperature of a mere 0.5 degrees to 2 degrees C can significantly worsen or improve, respectively, postischemic neurologic outcome. The purpose of the present study was to evaluate a novel approach of selectively cooling the brain during hypothermic CPB and subsequent rewarming. METHODS: Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled halothane (n = 8 per group). Normocapnia (alpha stat technique) and a blood pressure near 75 mm Hg were maintained. Temperatures were monitored by placing thermistors in the esophagus (i.e., core), parietal epidural space, and brain parenchyma at depths of 1 and 2 cm beneath the dura. During CPB, core temperature was actively cycled from 38 degrees C to 28 degrees C, and then returned to 38 degrees C. Forced air pericranial cooling (air temperature of approximately 13 degrees C) was initiated simultaneous with the onset of CPB, and maintained throughout the bypass period. Brain-to-core temperature gradients were calculated by subtracting the core temperature from regional brain temperatures. RESULTS: In halothane-anesthetized dogs, brain temperatures at all monitoring sites were significantly less than core during all phases of CPB, with one exception (2 cm during systemic cooling). Brain cooling was most prominent during and after systemic rewarming. For example, during systemic rewarming, average temperatures in the parietal epidural space, and 1 and 2 cm beneath the dura, were 3.3 degrees +/- 1.3 degrees C (mean +/- standard deviation), 3.2+/-1.4 degrees C, and 1.6 degrees +/-1.0 degrees C, cooler than the core, respectively. Similar trends, but of a greater magnitude, were noted in pentobarbital-anesthetized dogs. For example, during systemic rewarming, corresponding brain temperatures were 6.5 degrees +/-1.7 degrees C, 6.3 degrees +/-1.6 degrees C, and 4.2+/-1.3 degrees C cooler than the core, respectively. CONCLUSIONS: The magnitude of selective brain cooling observed in both study groups typically exceeded the 0.5 degrees to 2.0 degrees C change previously reported to modulate ischemic injury, and was most prominent during the latter phases of CPB. When compared with previous research from our laboratory, application of cold forced air to the cranial surface resulted in brain temperatures that were cooler than those observed during hypothermic CPB without pericranial cooling. On the basis of the assumption that similar beneficial brain temperature changes can be induced in humans, we speculate that selective convective brain cooling may enable clinicians to improve neurologic outcome after hypothermic CPB.     

Oral health week

This article reports on the Oral Health Week held in December 1994 and focuses on an initiative by the BDA which organised dentists and volunteers from Age Concern in a project to look at oral health for the elderly. It examines the aims and the results of the week and draws some useful conclusions on improving the outcome if a project such as this were attempted again.     

Differential effects of myeloperoxidase-derived oxidants on Escherichia coli DNA replication

The microbicidal myeloperoxidase (MPO)-H2O2-chloride system strongly inhibits Escherichia coli DNA synthesis. Also, cell envelopes from MPO-treated E. coli cells lose their ability to interact with hemimethylated DNA sequences of oriC, the chromosomal origin of replication, raising the prospect that suppression of DNA synthesis involves impairment of oriC-related functions (H. Rosen, et al. Proc. Natl. Acad. Sci. USA, 87:10048-10052, 1990). To evaluate whether origin-specific DNA sequences play a role in the MPO effect on E. coli DNA synthesis, plasmid DNA replication was compared to total (chromosomal) DNA replication for six plasmids with three distinct origins of replication. Plasmid pCM700 replication, replicating from oriC, was as sensitive to MPO-mediated inhibition as was total (chromosomal) DNA replication. A regression line describing this relationship had a slope of 0.90, and the r2 was 0.89. In contrast, the replication activities of three of four non-oriC plasmids, pUC19, pACYC184, and pSC101, demonstrated significant early resistance to inhibition by MPO-derived oxidants. The exception to this resistance pattern was plasmid pSP102, which has an origin derived from P1 phage. pSP102 replication declined similarly to that of total DNA synthesis. The regression line for pSP102 replication versus total DNA synthesis had a slope of 0.95, and the r2 was 0.92. The biochemical requirements for P1-mediated replication are strikingly similar to those for oriC-mediated replication. It is proposed that one of these requirements, common to oriC and the P1 origin but not critical to the replication of the other non-oriC plasmids, is an important target for MPO-mediated oxidations that mediate the initial decline in E. coli chromosomal DNA synthesis.     

Flaujeac factor deficiency. Reconstitution with highly purified bovine high molecular weight-kininogen and delineation of a new permeability-enhancing peptide released by plasma kallikrein from bovine high molecular weight-kininogen

Flaujeac trait is the functional deficiency of a plasma protein of the intrinsic coagulation, kinin-forming, and plasma fibrinolytic pathways. The Flaujeac factor in man has been isolated and tentatively identified as a kininogen of high molecular weight (HMW). Highly purified bovine HMW-kininogen, but not bovine low molecular weight kininogen, repaired Flaujeac factor deficiency. The two subspecies of this molecule, HMW-kininogen a and HMW-kininogen b, also corrected Flaujeac factor deficiency. When bovine HMW-kininogen was incubated with bovine plasma kallikrein, kinin-free HMW-kininogen, bradykinin, and a glycopeptide fragment (peptide 1-2; 12,584 daltons) were rapidly released. None of these fragmentation products corrected Flaujeac factor deficiency alone or in mixtures. The function of HMW-kininogen appeared to depend upon the structural integrity of the native molecule. When injected in concentrations of 2 pmol-8 nmol/0.1 ml, peptide 1-2 caused increased vascular permeability in rabbits, rats, or guinea pigs. The enhanced permeability was maximal within 1-2 min and terminated in 5-10 min, differing from that of bradykinin or histamine. Injected together in equimolar amounts, peptide 1-2 and bradykinin produced a synergistic permeability response which was immediate in onset as well as prolonged in duration. Peptide 1-2 is a rapidly acting, highly basic glyco-peptide which mediates increased vascular permeability in a complementary and synergistic manner with bradykinin.     

Prostaglandin E2 induction of labor for fetal demise

Intrauterine fetal demise is a source of anxiety to both patient and physician. Heretofore, the standard treatment was either careful observation until the patient went into labor or attempt at induction of labor with oxytocin. Unfortunately, oxytocin stimulation has not proven to be uniformly successful for this problem. Prostaglandin E2 suppositories have been shown to be effective in inducing uterine evacuation after intrauterine fetal demise. In the opinion of the authors, this approach will in the future replace the sometimes dangerous and emotionally laden convention of watchful delayed therapy.     

Aldosterone secretion during high sodium cerebrospinal fluid perfusion of the brain ventricles

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n=5) received perfusion with aritifical CSF containing NA 170 MEq./1, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./1, Group III (n=7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 +/- 7.4 to 8.6 +/- 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.