Biomedical subjects
Publications and source records attributed to E Hernandez.
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BACKGROUND: In ovarian carcinoma, DNA ploidy measured by flow cytometric (FCM) analysis is an independent prognostic factor. However, limited sampling may underestimate the extent of ploidy variation (i.e., heterogeneity). Uncovering these hidden populations may explain poor outcomes in patients with ostensibly favorable ploidy patterns. The authors examined ploidy in a mean of 6.4 tumor samples per patient to better assess the occurrence of heterogeneity. METHODS: FCM analysis was performed on multiple samples from 19 cases of advanced, serous ovarian carcinoma. Tumors were considered as heterogeneous by two definitions: (1) the presence of more than one ploidy pattern (e.g., diploidy and tetraploidy); and (2) the existence of DNA indices of sufficient variation so as to characterize two distinct populations of neoplastic cells. RESULTS: With the first definition, 47% (9 of 19) of the tumors were heterogeneous, 37% (7 of 19) homogeneous-aneuploid, and 16% (3 of 19) homogeneous-diploid. These three groups showed no significant differences in histologic type, grade, patient age, stage, or survival. With the second definition, 27% (4 of 15) of the non-diploid cases were heterogeneous and 73% (11 of 15) were homogeneous. When these two groups were compared as to type, grade, patient age, and stage, no significant differences were demonstrated. However, the median survival of the patients with heterogeneous tumors was significantly longer (P < 0.05) than the survival of patients with homogeneous tumors. CONCLUSIONS: Ovarian carcinoma heterogeneity is high when multiple sites are assayed. This suggests conservative interpretation of ploidy when only a single sample is analyzed and examination of multiple samples when practicable.
Levels of cAMP (23.1 pmol/ml) and cGMP (22.6 pmol/ml) are nearly equal in normal rabbit vitreous, although aqueous cAMP levels (29.9 pmol/ml) are 10 times higher than aqueous cGMP levels (2.6 pmol/ml) (P < 0.01). Intravitreal cAMP values decrease slightly 1 week after vitrectomy and lensectomy and return to normal whether the retina is attached, detached, or surgically removed. In contrast, intravitreal cGMP levels are profoundly depressed at 7 days (approximating normal aqueous levels) and are more than 50% lower than normal 30-42 days after surgery. The presence of these cyclic nucleotides in intraocular fluid and their responsiveness after surgery may signify a potential regulatory role in the physiologic responses of the eye to retinal detachment and its repair.
1. We characterized the basolateral membrane Cl- and K+ conductances of the dark-adapted chick neural retina-retinal pigment epithelium (RPE)-choroid preparation. Conventional microelectrodes were used to measure apical (V(ap)) and basolateral (Vba) membrane voltage, and double-barreled Cl- and K+ selective microelectrodes were used to follow the time course and magnitude of ion concentration changes outside the basolateral (basal) membrane. 2. In response to a fivefold decrease in basal [Cl-]o, Vba rapidly depolarized by 6.4 +/- 0.7 (SE) mV, and the apparent resistance of the basolateral membrane (Rba) increased. The Cl- channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) suppressed the Vba depolarization by 40% and blocked the Rba increase. Estimates of the relative Cl- conductance (transference number, TCl) from the DIDS-sensitive component of the Cl- diffusion potential gave an average value for TCl of 0.22 +/- 0.03. 3. Further evidence for a Cl- conductance was obtained by measuring changes in intracellular Cl- activity (aCli) induced by transtissue current. Depolarizing Vba elevated aiCl, whereas hyperpolarizing Vba had the opposite effect, consistent with conductive Cl- movement across the basal membrane. TCl estimated from these data averaged 0.23 +/- 0.02. 4. In response to a sixfold increase in basal [K+]o, Vba depolarized 6.1 +/- 0.8 mV. The amplitude of this K+ diffusion potential was inhibited 44 and 67% by 5 and 10 mM Ba2+, respectively. TK was estimated to be 0.61 +/- 0.05. 5. The rapid c-wave membrane hyperpolarizations in response to the light-evoked decrease in subretinal [K+]o were used to calculate the equivalent resistances of the apical membrane (R(ap)), basolateral membrane (Rba), and the paracellular shunt pathway (Rs). They were 152 +/- 10, 615 +/- 38, and 138 +/- 7 omega.cm2 (n = 11 tissues), respectively. From these data the equivalent electromotive force for the basal (Eba) and apical (Eap) membranes were estimated to be -45 +/- 2 and -77 +/- 1 mV, respectively. This estimate of Eba is in the range of that predicted from our estimates of TCl and TK, indicating that, in the dark-adapted chick retina, the resting conductance of the basal membrane can largely be accounted for by the Cl- and K+ conductances described here.
Accidental hypothermia is defined as a spontaneous decrease in core temperature to 35 degrees C or below. Several techniques of active core rewarming have been described. We present the case of a 34-year-old man with severe hypothermia (27 degrees C) caused by cold environment exposure and barbiturate intoxication treated with general supportive measures and active core rewarming with hemodialysis. Core temperature increased by 2.15 degrees C/h with hemodialysis and became normal in 4 h. The clinical situation clearly improved during the hemodialysis session and the patient recovered without any defect. Hemodialysis is a rapid and effective treatment for accidental hypothermia.
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This review examines methods of assessing the prognosis of uterine tumors published in the past year. Evaluation of mitosis counts has shown that mitotically active leiomyomas without cytologic atypia follow a benign course; furthermore, the mitotic index does not differentiate endometrial hyperplasia from adenocarcinoma. 'Vascular invasion-associated changes' (VIAC) have been identified as a new prognostic factor for stage 1 endometrial adenocarcinoma. HER-2/neu oncogene expression is also a major prognostic factor in endometrial carcinoma, but positive peritoneal cytology influences survival only in the presence of extrauterine disease. Frozen-section diagnosis and curettings findings at the time of surgery identify poor prognostic factors, allowing limited surgery in patients without poor prognostic indicators. Finally, DNA ploidy as determined by flow cytometry was of prognostic value in uterine sarcomas in one study but not in another when endometrial stromal sarcomas were analysed separately.
Use of the nylon endocervical brush has been shown to increase the proportion of Papanicolaou smears with endocervical cells in a variety of populations. Each endocervical brush is approximately 100 times more expensive than the cotton swab that has been used routinely for cervical cytology collection. We sought to determine prospectively whether the endocervical brush would be cost effective by reducing the need for repeat sampling due to Papanicolaou smears' lacking endocervical cells. Cervical cytology specimens showed no endocervical cells in 114 (20%) of 561 women sampled with a cotton swab and Ayre spatula. In contrast, 37 (7%) of 511 women sampled with the endocervical brush and Ayre spatula had no endocervical cells in their specimens. A cost analysis showed that at our clinic, where approximately 3,300 Papanicolaou smears are performed annually, annual savings of > $22,000 would be realized by use of endocervical brushes.
The medical records of 113 patients treated with radiation therapy for invasive cervical cancer between 1975 and 1985 were retrospectively reviewed. Patients with thrombocytosis (platelet count greater than 400,000/microliters) were compared with those with normal platelet counts. Thrombocytosis was present at the initiation of therapy in 20 (17.7%) of the 113 patients. The 5-year cumulative survival rate for the 93 patients with normal platelet counts was 65%, whereas it was 25% for the 20 with thrombocytosis (P less than 0.0001, log-rank test). Using Cox's proportional hazards model, thrombocytosis continued to correlate strongly with poor survival even when adjusted for histologic type, patient age, and disease stage (P less than 0.001). Thrombocytosis is an independent indicator of poor prognosis in patients with cervical cancer.
Diode laser photocoagulation was applied to rabbit retina simulating scatter treatment using an endolaser probe and in a manner simulating treatment of peripheral retinal breaks using a transscleral retinopexy probe. Clinically appearing mild, moderate, and severe burns were created by altering the burn duration in one eye and by altering the power setting in the fellow eye. Histopathologic results demonstrated the clinically evident dose-response effect with sparing of inner retinal cellular elements with mild burns and full-thickness retinal cell loss with severe burns. Bruch's membrane ruptures were seen in three of 42 endophotocoagulation severe spots placed with high power, but in none of the 42 severe spots placed with long burn duration. Thus, longer burn duration appeared to be a safer way to produce a severe burn than higher power. Burns characteristically bloomed during the several seconds following laser application by both modalities, possibly indicating a deep source of energy absorption. Scleral effects, seen only when high energy levels were used to treat atrophic areas, were mild.
A retinal break and localized retinal detachment were induced in 10 rabbit eyes. The retinal break was treated within regions of detached retina using diode laser transscleral retinopexy (four eyes), diode laser indirect ophthalmoscopy (two eyes), or retinocryopexy (two eyes). Two eyes were left as untreated controls. The clinical and histopathologic effects were studied 1 day and 3 weeks after initial treatment. Suitable chorioretinal adhesions were induced with all treatment modalities. The extent of tissue effects was greater in cryopexy and smaller in laser treatment. The histopathologic characteristics of the lesions induced by diode laser indirect ophthalmoscopy were similar to those seen with transscleral diode treatment and were more focal than those seen with cryopexy. Transscleral and transpupillary diode laser photocoagulation were effective in inducing chorioretinal adhesions in detached retina in this experimental model in rabbits.
Cellular proliferation is an important component in the pathogenesis of complex retinal detachments caused by proliferative vitreoretinopathy (PVR). We used flow cytometry to measure the proliferation of cells recovered from the vitreous cavity in an experimental model of tractional retinal detachment induced by homologous fibroblast injection. Two distinct populations of cells were detected. One population comprised smaller, dense cells representing mostly leukocytes. A second population of larger cells contained not only the injected fibroblasts but also high concentrations of host-derived cells with significant proliferative activity, whose number increased for 3 days following injection. Flow cytometry was useful for analysis of the recovered cells for concentration, morphologic features and proliferation. This technique may be applicable in the identification of patients at high risk for the development of PVR.
Ethisolide has been isolated from cultures of Penicillium capsulatum, and its structure determined by means of infrared, mass spectrometry, 1H- and 13C nuclear magnetic resonance. Antibiotic activity against a number of microorganisms is reported.
To assess the role for intraoperative thrombolysis during surgical evacuation of massive subretinal hemorrhage, the authors studied the ability of tissue plasminogen activator (tPA) to facilitate removal of an experimental subretinal blood clot through a small drainage retinotomy. In rabbit eyes, a single subretinal injection of tissue plasminogen activator in concentrations of up to 250 micrograms/ml failed to produce significant (greater than 50%) clot dissolution during a 3-hour period. However, repetitive subretinal lavage and aspiration with tPA (50 micrograms/ml) resulted in progressive intraoperative clot dissolution in rabbits and allowed complete evacuation of blood through a small drainage retinotomy in 6 (100%) of 6 cat eyes. Repetitive vigorous subretinal irrigation with saline solution had no discernible effect on clot size in rabbit eyes. Histopathologic examination of cat eyes following tPA-assisted surgical evacuation of subretinal blood showed preservation of the outer retina in 2 eyes and severe atrophy of the outer retina in 4 eyes.
In the attempt to define the characteristics of a global approach to the problem of atmospheric pollution, the mathematical and statisticals tools currently available are presented which will allow the rationalization of both the study and the management of reduction policy. An example of a possible application of this approach is given, which presents the results obtained by modelling the data on "conventional" pollutants furnished by the experimental sampling station set up at the Istituto Superiore di Sanità (ISS) in Rome. Since the suggested approach may not do without an integrated management of date, a hypothesis for an information system is outlined as well.
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The retinal toxicity of human tissue plasminogen activator in normal rabbit eyes has recently been reported. We now report the retinal toxicity of tissue plasminogen activator in three groups of vitrectomized rabbit eyes. Group 1 underwent gas compression of the vitreous followed by tissue plasminogen activator injection in doses of 25, 50, and 100 micrograms (all doses were administered in 100 microL of fluid). Group 2 underwent lensectomy and vitrectomy followed by tissue plasminogen activator injection of 100 micrograms. Group 3 underwent lensectomy, vitrectomy, and complete fluid/gas exchange prior to injections of 12.5 and 25 micrograms of tissue plasminogen activator. Control eyes received 100 microL of balanced salt solution. In group 1, no retinal toxic reactions were observed after administration of 25 or 50 micrograms of tissue plasminogen activator, but all eyes receiving 100 micrograms demonstrated retinal damage on ophthalmoscopy, electroretinography, and light microscopy. In group 2, no retinal toxic reactions were seen after administration of 100 micrograms of tissue plasminogen activator. In group 3, two of 11 eyes receiving 25 micrograms of tissue plasminogen activator demonstrated toxic retinal changes by ophthalmoscopy, electroretinography, and light microscopy. These results suggest that gas compression of the vitreous does not significantly alter the toxic changes seen caused by tissue plasminogen activator. While lensectomy and vitrectomy appears to widen the therapeutic window for tissue plasminogen activator, the margin of safety is reduced with the addition of a large gas bubble.