Simplified biplanar (0-90°) fluoroscopic puncture technique for percutaneous nephrolithotomy: the learning curve.

PURPOSE: To evaluate the learning curve of the simplified fluoroscopic biplanar (0-90º) puncture technique for percutaneous nephrolithotomy. METHODS: We prospectively evaluated patients with renal stones treated with percutaneous nephrolithotomy by a single institution's fellows employing the simplified bi-planar (0-90º) fluoroscopic puncture technique for renal access. The learning curve was assessed with the fluoroscopic screening time and the percutaneous renal puncture time. Data obtained were compared to a subset of patients operated by a senior surgeon. RESULTS: Eighty-nine patients were included in the study. Forty patients were operated by fellow-1, 39 by fellow-2, and 10 patients by the senior surgeon. Demographic data of all patients between groups were homogeneous, with no difference in gender (p = 0.432), age (p = 0.92), stone volume (p = 0.78), puncture laterality (p = 0.755), and body mass index (p = 0.365). The mean puncture time was 7.5, 4, and 3.1 min for fellow-1, fellow-2, and expert, respectively. The mean fluoroscopic screening time for the puncture was 10, 11, and 5.1 s for fellow-1, fellow-2, and the expert, respectively. Stone cases, both fellows needed to complete 10 procedures to match the senior surgeon in the mean puncture time (p = 0.046); meanwhile, the fluoroscopic screening time was equal even before to complete 10 procedures. CONCLUSION: This study suggests that with the simplified biplanar (0-90º) puncture technique, the fluoroscopic screening time used in the learning process is brief. A novice fellow could require to complete ten cases to flatten the learning curve treating complex stone cases, and a flat learning curve is seen since the beginning when treating simple renal stones.

Distribution of repetitive DNAs and the hybrid origin of the red vizcacha rat (Octodontidae).

Great genome size (GS) variations described in desert-specialist octodontid rodents include diploid species ( Octomys mimax and Octodontomys gliroides ) and putative tetraploid species ( Tympanoctomys barrerae and Pipanacoctomys aureus ). Because of its high DNA content, elevated chromosome number, and gigas effect, the genome of T. barrerae is claimed to have resulted from tetraploidy. Alternatively, the origin of its GS has been attributed to the accumulation of repetitive sequences. To better characterize the extent and origin of these repetitive DNA, self-genomic in situ hybridization (self-GISH), whole-comparative genomic hybridization (W-CGH), and conventional GISH were conducted in mitotic and meiotic chromosomes. Self-GISH on T. barrerae mitotic plates together with comparative self-GISH (using its closest relatives) discriminate a pericentromeric and a telomeric DNA fraction. As most of the repetitive sequences are pericentromeric, it seems that the large GS of T. barrerae is not due to highly repeated sequences accumulated along chromosomes arms. W-CGH using red-labeled P. aureus DNA and green-labeled O. mimax DNA simultaneously on chromosomes of T. barrerae revealed a yellow-orange fluorescence over a repetitive fraction of the karyotype. However, distinctive red-only fluorescent signals were also detected at some centromeres and telomeres, indicating closer homology with the DNA sequences of P. aureus. Conventional GISH using an excess of blocking DNA from either P. aureus or O. mimax labeled only a fraction of the T. barrerae genome, indicating its double genome composition. These data point to a hybrid nature of the T. barrerae karyotype, suggesting a hybridization event in the origin of this species.

Neuronal cell death due to glutamate excitotocity is mediated by p38 activation in the rat cerebral cortex.

Excitotoxic neuronal death occurs through the activation of NMDA and non-NMDA glutamatergic receptors in the CNS. Glutamate also induces strong activation of p38 and indeed, cell death can be prevented by inhibitors of the p38 pathway. Furthermore, intracellular signals generated by AMPA receptors activate the stress sensitive MAP kinases implicated in apoptotic neuronal death, such as JNK and p38. To investigate the relationship between these elements, we have used immunohistochemistry to analyze the expression of GluR2 in the cerebral cortex of postnatal rats (postnatal Day [PD] 8 and 14) after administering them with monosodium glutamate (MSG; 4 mg/g body weight on PD1, 3, 5, and 7). Similarly, the expression of REST, Fas-L and Bcl-2 mRNA transcripts in animals exposed to a p38 inhibitor, SB203580 (0.42 microg/g body weight, administered subcutaneously) was determined by reverse transcriptase-PCR. The enhanced GluR2-expression in the cerebral cortex at PD8 and the down regulation of this receptor at PD14 was correlated with neuronal damage induced by excitotoxicity. In addition, the enhanced expression of REST at PD8 and PD14 suggests that the induction of REST transcription contributes to glutamate-induced excitotoxic neurodegeneration, possibly by modulating GluR2 expression. Fas-L and Bcl-2 over expression at PD8 and their subsequent down regulation at PD14 also suggests that Fas-L could be the direct effector of apoptosis in the cerebral cortex. On the other hand, the presence of Bcl-2 at PD8 could attenuate certain survival signals in neurons under these neurotoxic conditions. Thus, a change in glutamate receptor composition, and enhanced Fas-L and Bcl-2 expression, coupled with activation of the p38/SAPK pathway appear to be events involved in the neuronal apoptosis induced under neurotoxic conditions.

Herpes simplex virus type 2 and human cervical cancer: relationship between cellular and immune assays for the detection of previous infection.

Women with invasive carcinoma of the cervix were examined for evidence of previous infection with herpes simplex virus (HSV) type 2 (HSV-2) by three assays: Assay 1 measured the ratio of lymphocyte blastogenesis to herpes simplex virus type 1 (HSV-1) and HSV-2 antigens; assay 2 measured the ratio of antibody titer to surface antigens of HSV-1-infected and HSV-2-infected cells; assay 3 measured the titer of type-specific antibody to HSV-1 and HSV-2, including the percentage of HSV-2 type-specific to total HSV antibody. The ability of assays to detect previous infection was evaluated with the use of groups with histories of infection with HSV-1, HSV-2, or both. Women with invasive cervical cancer were matched to control women by age (+/- 3 yr), race (black), and socioeconomic class (low). All assays detected similar patterns of previous HSV-2 infection, and all indicated a higher frequency of previous HSV-2 infection in women having cervical cancer. Results from assays 1 and 2 suggest that many of the cancer patients and controls also had been infected with HSV-1. The more definitive type-specific antibody assay confirmed those results and showed that sera from 85% of women having cervical cancer and from 100% of the matched controls contained antibody type-specific for HSV-1.

Selective inhibitors of human lactate dehydrogenases and lactate dehydrogenase from the malarial parasite Plasmodium falciparum.

Derivatives of the sesquiterpene 8-deoxyhemigossylic acid (2, 3-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthoic acid) were synthesized that contained altered alkyl groups in the 4-position and contained alkyl or aralkyl groups in the 7-position. These substituted dihydroxynaphthoic acids are selective inhibitors of human lactate dehydrogenase-H (LDH-H) and LDH-M and of lactate dehydrogenase from the malarial parasite Plasmodium falciparum (pLDH). All inhibitors are competitive with the binding of NADH. Selectivity for LDH-H, LDH-M, or pLDH is strongly dependent upon the groups that are in the 4- and 7-positions of the dihydroxynaphthoic acid backbone. Dissociation constants as low as 50 nM were observed, with selectivity as high as 400-fold.

Nitric oxide synthase isoforms and peripheral chemoreceptor stimulation in conscious rats.

To test the effect of nitric oxide synthase (NOS) blockade on the ventilatory responses to carotid body chemoreceptor stimulation in freely behaving animals, chronically instrumented adult Sprague-Dawley rats received increasing intravenous doses of sodium cyanide (NaCN; 0-300 micrograms kg-1) before and after i.v. administration of either 100 mg kg-1 N-nitro-L-arginine methyl ester (L-NAME), a non-specific NOS blocker, or 10 mg kg-1 S-methyl-L-thiocitrulline (SMTC), a selective neuronal NOS inhibitor. SMTC did not modify the NaCN dose-response curve. In contrast, L-NAME significantly enhanced the ventilatory responses to NaCN. Western blots of equivalent amounts of protein from carotid body tissue homogenates revealed higher levels of endothelial NOS than of neuronal NOS. We conclude that endothelial NOS provides the major source for NO within the carotid body, and exerts a down-regulatory effect upon peripheral chemoreceptor responsivity.

Effect of nitric oxide synthase inhibition on cardiorespiratory responses in the conscious rat.

Nitric oxide synthase (NOS) blockade was used to test the cardioventilatory responses to hypercapnia and hypoxia in freely behaving animals. Chronically instrumented adult Sprague-Dawley rats were studied before and after intravenous administration of either 100 mg/kg of NG-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS blocker, or 10 mg/kg of S-methyl-L-thiocitrulline (SMTC), a selective neural NOS inhibitor. L-NAME injection induced sustained blood pressure (BP) elevation with transient tachycardia and increased minute ventilation (VE), which returned to baseline within minutes. SMTC elicited similar, although transient, BP increases; however, heart rate and VE decreased. L-NAME and SMTC did not modify overall steady-state hypercapnic responses. In control conditions, hypoxia induced early VE increases with further VE enhancements at 30 min. L-NAME increased the early VE response to 10% O2 but induced late VE reductions in hypoxia. SMTC did not change early VE responses but induced marked reductions in the later VE hypoxic responses. In control animals, hypoxia induced a significant heart rate increase. This increase was absent during the early response after SMTC and was followed in both L-NAME- and SMTC-treated animals by significant heart rate reductions to values below room air. Similarly, the sustained BP response to hypoxia in control animals was absent after administration of NOS inhibitors. These findings suggest that NOS activity exerts excitatory influences on respiration and cardiac chronotropy and sustained vasomotor tone during hypoxia. We speculate that NOS-mediated mechanisms may play an important role in hypoxia-induced ventilatory roll-off during wakefulness.

Short-term potentiation of ventilation after different levels of hypoxia.

Short-term potentiation of ventilation (VSTP) may be observed in healthy subjects on sudden termination of an hypoxic stimulus. We hypothesized that the level of hypoxia preceding normoxia would modify the duration and magnitude of the ensuing ventilatory decay. Ten healthy adults were studied on two different occasions, during which they were randomly exposed to isocapnic 6 or 10% O2 for 60 s and then switched to an isocapnic normoxic gas mixture. Both hypoxic gases induced significant ventilatory responses, and mean peak minute ventilation before the isocapnic normoxic switch was higher in 6% O2 (P < 0.001). The fast time constant of the two-exponential equation representing the best fit for ventilatory decay was unaffected by the magnitude of the hypoxic stimulus. However, the slow time constant, which is considered to represent VSTP, was markedly prolonged in 6% compared with 10% O2 [106.7 +/- 11.3 vs. 38. 2 +/- 6.1 (SD) s, respectively; P < 0.0001]. This result indicates that VSTP is stimulus dependent. We conclude that the magnitude of hypoxia preceding a normoxic transient modifies VSTP characteristics. We speculate that the interdependence function of ventilatory stimulus and short-term potentiation is crucial for preservation of system stability during transitions from high to low ventilatory drives.

NMDA receptors mediate peripheral chemoreceptor afferent input in the conscious rat.

N-methyl-D-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (VE) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (VT) decreased while frequency increased, resulting in a modest reduction in VE. Inspiratory time (TI) decreased, whereas expiratory time remained unchanged. The VE responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (VT/TI) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas VT was unaffected. Sodium cyanide doses associated with significant VE increases were 5 and 50 microg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reduced VE during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.

Protein kinase C modulation of ventilatory response to hypoxia in nucleus tractus solitarii of conscious rats.

This study aimed to determine the role of protein kinase C (PKC) in signal transduction mechanisms underlying ventilatory regulation in the nucleus tractus solitarii (NTS). Microinjection of phorbol 12-myristate 13-acetate into the commissural NTS of nine chronically instrumented, unrestrained rats elicited significant cardiorespiratory enhancements that lasted for at least 4 h, whereas administration of vehicle (n = 15) or the inactive phorbol ester 4alpha-phorbol 12,13-didecanoate (n = 7) did not elicit minute ventilation (VE) changes. Peak hypoxic VE responses (10% O2-balance N2) were measured in 19 additional animals after NTS microinjection of bisindolylmaleimide (BIM) I, a selective PKC inhibitor (n = 12), BIM V (inactive analog; n = 7), or vehicle (Con; n = 19). In Con, VE increased from 139 +/- 9 to 285 +/- 26 ml/min in room air and hypoxia, respectively, and similar responses occurred after BIM V. BIM I did not affect room air VE but markedly attenuated hypoxia-induced VE increases (128 +/- 12 to 167 +/- 18 ml/min; P < 0. 02 vs. Con and BIM V). When BIM I was microinjected into the cerebellum (n = 4), cortex (n = 4), or spinal cord (n = 4), VE responses were similar to Con. Western blots of subcellular fractions of dorsocaudal brain stem lysates revealed translocation of PKCalpha, beta, gamma, delta, epsilon, and iota isoenzymes during acute hypoxia, and enhanced overall PKC activity was confirmed in the particulate fraction of dorsocaudal brain stem lysates harvested after acute hypoxia. These studies suggest that, in the adult rat, PKC activation in the NTS mediates essential components of the acute hypoxic ventilatory response.

Cardiorespiratory responses to systemic administration of a protein kinase C inhibitor in conscious rats.

Although protein kinase C (PKC) is an essential component of multiple neurally mediated events, its role in respiratory control remains undefined. The ventilatory effects of a systemically active PKC inhibitor (Ro-32-0432; 100 mg/kg i.p.) were assessed by whole body plethysmography during normoxia, hypoxia (10% O2), and hyperoxia (100% O2) in unrestrained Sprague-Dawley rats. A sustained expiratory time increase occurred within 8-10 min of injection in room air[mean 44.8 +/- 5.2 (SE) % ], was similar to expiratory time prolongations after Ro-32-0432 administration during 100% O2 (45.5 +/- 8.1%; not significant), and was associated with mild minute ventilation (VE) decreases. Hypercapnic ventilatory responses (5% CO2) remained unchanged after Ro-32-0432. During 10% O2, VE increased from 122.6 +/- 15.6 to 195.7 +/- 10.1 ml/min in vehicle-treated rats (P < 0.001). In contrast, marked attenuation of VE hypoxic responses occurred after Ro-32-0432 [86.2 +/- 6.2 ml/min in room air to 104.1 +/- 7.1 ml/min in 10% O2; pre- vs. post-Ro32-0432, P < 0.001 (analysis of variance)]. Overall, PKC activity was reduced and increases with hypoxia were abolished in the particulate subcellular fraction of brain tissue after Ro-32-0432 treatment, indicating that this compound readily crosses the blood-brain barrier. We conclude that systemic PKC inhibition elicits significant centrally mediated expiratory prolongations and ventilatory reductions as well as blunted ventilatory responses to hypoxia but not to hypercapnia. We postulate that PKC plays an important role in signal transduction pathways within brain regions underlying respiratory control.

Nitric oxide modulates in vitro intrinsic optical signal and neural activity in the nucleus tractus solitarius of the rat.

Nitric oxide (NO) is a novel neurotransmitter with important cardiorespiratory functions. To determine the functional topography of NO in a brainstem preparation, extracellular and intrinsic optical signal recordings were simultaneously acquired from a 300 microm coronal brainstem slice at the level of the obex. During control conditions, spontaneous spike activity in the nucleus tractus solitarius (NTS) was 6.2 +/- 1.4 Hz. When the competitive NOS inhibitor, L-NAME, was applied to the bath (1 mM), spike activity either ceased or was markedly reduced in frequency (1.2 +/- 0.7 Hz; n = 7; P < 0.01). The decrease in activity was reversed when the NOS substrate L-arginine (L-Arg) was added to the bath (9.4 +/- 1.8 Hz; P < 0.04). Concurrent intrinsic optical signal imaging of the slice preparation consistently revealed coincident decreases in activity within the NTS with L-NAME (deltaT/T: -2.4 +/- 0.9%; P < 0.02), and increases with L-Arg (+2.1 +/- 0.8%; P < 0.04). Such changes were absent in other regions such as the hypoglossal nuclei or area postrema. We conclude that in this brainstem region, NO modulation of neuronal activity is primarily circumscribed to the NTS.

History of colposcopy in the United States. Chronology of colposcopy development worldwide.

Colposcopy was initially developed by Professor Hinselmann of Germany and is now a procedure that is recognized the world over. Twenty-two countries now represent the International Federation for Cervical Pathology and Colposcopy. Additionally, individual societies representing several countries exist.

Colposcopy screening for cervical cancer in a family planning program.

A brief history is presented of colposcopy in the United States and at Louisiana State University. Incorporation of colposcopy screening as a part of the cervical cancer screening program in the Louisiana Family Planning Program is discussed, and the reasons for the need of "in house" colposcopy service are outlined. Data of the Louisiana Family Planning Program Colposcopy Service for the three-year period 1972 through 1974 are presented. Analysis of these data reveals that cytology when used without colposcopy fails to reveal the presence of major cervical pathology in 30.2% of patients. It is concluded that colposcopic screening must be a part of all family planning and cervical cancer detection programs.

PIP: A history of colposcopy in the United States is presented. The first colposcopic clinics were in Philadelphia (1952-1953) and in Louisiana (1954). The importance of colposcopy screening as a part of the cervical cancer screening program is explained as well as the necessity for an "in house" colposcopy service. The data of the Louisiana Family Planning Program Colposcopy Service show that when used without colposcopy, cytology fails to reveal major cervical pathology in 30.2% of the cases. Thus combining colposcopic screening with cytology helps detect patients with major cervical pathology. Therefore it is necessary that colposcopic screening be a part of family planning and cervical cancer detection programs.

Colposcopically directed conization for frozen-section examination in the management of cervical intraepithelial neoplasia.

We found colposcopically directed conization for frozen-section (F/S) examination to be 100% accurate in ruling out the presence of invasive cervical carcinoma. Therefore, the definitive treatment for cervical intraepithelial neoplasia (CIN)--hysterectomy in women who do not want more children--could be performed while the patient was still under the anesthetic used during procurement of the conization specimen. This technique reduces the risk of using anesthesia a second time and also reduces the costs of CIN treatment. Colposcopically directed conization should be done by experienced colposcopists only.

Bile salt-stimulated lipase in the milk of Fulani and Kanuri women in Nigeria and native Nepalese women.

Human milk provides newborns with several physiologically important proteins not found in cow's milk, including bile salt-stimulated lipase (BSSL) that compensates for the reduced lipolytic capability of the newborn intestine. We analyzed the milk of two ethnically distinct groups of women in northern Nigeria and Nepal. The milk of the Nepalese women (n = 36) contained slightly more BSSL activity (mean, 38.8 units/mL) than that of Fulani (n = 48; mean, 30.3 units/mL) and Kanuri (n = 90; mean 27.6 units/mL) women in Nigeria. There was also a weak positive correlation between the BSSL content of the milk and the body mass index (BMI) of the lactating women. The BSSL activity declined with the length of lactation for both well-nourished and undernourished women. The presence of a heat-stable inhibitor of BSSL in cow's milk was also demonstrated. This finding, along with the decrease in BSSL activity postgestation, could be of significance to populations such as the Fulani of the western Sahel who supplement the diets of their infants with unpasteurized cow's milk.

Acquired nevus flammeus.

This is the case of a 55-year-old male with cirrhosis who required a LeVeen shunt for relief of refractory ascites. After eight months he developed recurrence of the ascites and a erythematous patch around the surgical scar. Skin biopsy revealed a proliferation of small and medium-sized vessels throughout the dermis. The acquired form of nevus flammeus is rare an is usually preceded by trauma. This is the report of a patient with an acquired nevus flammeus associated to an obstructed peritoneovenous shunt.

Response to treatment and recurrence of dermatomycosis in patients with diabetes.

Thirteen diabetic and sixteen control patients with skin infections with dermatophytes and Candida albicans were evaluated for the response to treatment and the recurrence of the condition. Culture-proven infections of these organisms were treated with a topical antifungal cream (oxiconazole nitrate) for 30 days. There was no difference in response to treatment between the two groups. Nine diabetic and ten control patients were re-evaluated three months after finishing the treatment. Four of the nine diabetic patients (44%) and one of the ten control patients (10% had evidence of recurrence. Dermatophytic skin infections in diabetic patients seem to respond adequately to topical treatment, however, recurrences appear to be frequent.

Eccrine angiomatous hamartoma.

This is the case of a 13 year-old female evaluated for a congenital skin lesion on the left buttock. Physical examination revealed a well-defined light brown patch with a 4mm papule on the center. A skin biopsy revealed an increased number of eccrine glands associated to a proliferation of vascular channels, particularly capillaries. These findings are consistent with a diagnosis of eccrine angiomatous hamartoma.

[The current status in obtaining a license for the practice of dentistry in the European Union and the United States of America]. / Estado actual de la obtención de la licencia para el ejercicio de la odontología en la Unión Europea y en los Estados Unidos de Norteamérica.

Present regulations on the issuance of dental licenses are very different between the United States of America and the European Community. Two different mechanisms attempt to arrive at the fairest possible solution: licenses controlled by either national and/or local examinations in the United States, and licensing by credentials in the European Community. Both are compared and discussed.