Water entrapment and structure ordering as protection mechanisms for protein structural preservation.

In this paper, molecular dynamics is used to further gain insight into the mechanisms by which typical pharmaceutical excipients preserve the protein structure. More specifically, the water entrapment scenario will be analyzed, which states that excipients form a cage around the protein, entrapping and slowing water molecules. Human growth hormone will be used as a model protein, but the results obtained are generally applicable. We will show that water entrapment, as well as the other mechanisms of protein stabilization in the dried state proposed so far, may be related to the formation of a dense hydrogen bonding network between excipient molecules. We will also present a simple phenomenological model capable of explaining the behavior and stabilizing effect provided by typical cryo- and lyo-protectants. This model uses, as input data, molecular properties which can be easily evaluated. We will finally show that the model predictions compare fairly well with experimental data.

Cardiovascular changes in patients with primary aldosteronism after surgical or medical treatment.

BACKGROUND: Data on the cardiovascular middle-term follow-up of patients with primary aldosteronism (PA) are scanty. AIM: To detect the cardiovascular effects of surgery in patients with aldosterone (ALD)-producing adenoma (APA) and of pharmacotherapy in those with bilateral adrenal hyperplasia (BAH), a prospective study involving 60 consecutive patients with PA was performed. MATERIAL/ METHODS: Clinical, biochemical, and cardiovascular assessment was obtained before and after (31.5±4.4 months) surgery or proper medical treatment (32.1±5.0 months) in 19 and 41 patients, respectively. RESULTS: As expected, plasma ALD normalized in all operated patients, while in the other group it did not change. Systolic and diastolic blood pressure decreased (p<0.001) after both treatments. However, absolute and percentage reduction was significantly more pronounced (p<0.01) in operated than in non-operated patients. Left ventricular (LV) mass showed significant reduction after surgery (LV mass g/m(2), p<0.0007; LV mass g/m(2.7), p<0.01), but no change after medical treatment, so that the differences between absolute and percentage values at follow- up were statistically significant (p<0.01) between groups. Basal LV mass/m(2.7) was positively associated with age (p<0.009), body mass index (p<0.0008), drug number (p<0.03), and ALD/plasma renin activity ratio (p<0.01). Allocating the patients according to plasma ALD and cardiac parameters, patients who presented ALD reduction during the study also had a decrement in cardiac mass (p<0.04). CONCLUSIONS: Our data indicate that in patients with PA the removal of ALD excess by surgery in APA is effective in reducing blood pressure and in improving cardiac parameters, while anti-hypertensive therapy in BAH shows less positive impact on cardiovascular system.

[Potential sources of diagnostic pitfall and variants in FDG-PET/CT]. / Potenciales fuentes de error diagnóstico y variantes de la FDG-PET/TAC.

UNLABELLED: Oncological FDG PET show variants and findings that may lead to a diagnostic error and that may be clarified by the morfofunctional imaging from PET/CT. In this article we show the experience acquired since a Siemens PET/CT Biograph LSO Pico3D was applied in our centre. We describe some representative examples of FDG distribution patterns which may lead to erroneous interpretations of the clinical studies when they refer to specific clinical situations. The examples included are classified into two main groups according to the cause: Technical and biological, and the latter into physiological and non-physiological (pathophysiological). Patterns are described within the biological group showing changes of the FDG biodistribution that may reduce the uptake in tumoural lesions, the physiological variants that may be interpreted as pathology, the effects of previous treatment and uptakes related to benign diseases. CONCLUSION: We consider that knowledge of these variants and findings to be crucial in order to obtain optimal performance of PET/CT and to overcome the PET limitations.

[Assessment of cerebral blood flow in patients with eating disorders in the acute clinical phase using Tc99m-HMPAO spect]. / Valoración del flujo sanguíneo cerebral en pacientes con trastornos de la conducta alimentaria en fase aguda mediante SPECT con HMPAO-Tc99m.

OBJECTIVE: To assess the status of cerebral perfusion in patients with eating disorders (ED) in the acute phase of the disease. MATERIALS AND METHODS: Seventeen patients, with a mean age of 22 years, diagnosed with ED according to DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) criteria and under close clinical monitoring were studied in the initial acute phase of their disease. Brain SPECT with 15 mCi of Tc99m HMPAO was performed on all patients and assessed using visual and semi-quantitative analysis. The latter was carried out by obtaining left/right indices in sixteen symmetrical 5 x 5 pixel regions of interest (ROI) in three transverse slices, one below the cantho-meatal line and two above, at 2 and 5 cm, respectively. RESULTS; Visual analysis showed hypoperfusion of the anteroinferior region of the left temporal lobe in 7/17 patients, and in the homonymous region of the right temporal lobe in 1/17. Semi-quantitative analysis did not show statistically significant differences in the slices above the cantho-meatal line when the means of the asymmetry indices were compared between the anterior (frontal), middle (temporal and parietal) and posterior (occipital) regions of each slice, obtaining values ranging between 0.99 +/- 0.05 and 1.02 +/- 0.03. However, in the lowest slice, the anterior (temporal) region showed a mean asymmetry value of 0.89 +/- 0.15, and on comparing it with the mean of the asymmetry indices of the posterior region (cerebellum), it showed a statistically significant difference (p < 0.05). CONCLUSION: Patients with ED frequently show hypoperfusion of the anteroinferior region of the temporal lobe, predominantly in the left hemisphere, in the acute phase of the illness.

Extensive intestinal metaplasia in gastric carcinoma and in other lesions requiring surgery: a study of 3,421 gastrectomy specimens from dwellers of the Atlantic and Pacific basins.

BACKGROUND: Extensive intestinal metaplasia (EIM) has been reported in gastrectomies from patients dwelling in the Pacific and Atlantic basins. AIMS: To compare all the results in an attempt to explain the findings. METHOD: All sections from 3,421 gastrectomies were reviewed at various hospitals: 1946 in the Atlantic and 1475 in the Pacific basin. Sections with EIM showed IM encompassing one or more entire low power field (>or=5 mm in length/section) in one or more section. RESULTS: In the Atlantic basin, EIM was present in 18.8% (153 of 814) of specimens with intestinal carcinoma (IC) and in 10.3% (65 of 630) of those with diffuse carcinoma (DC). In the Pacific basin, EIM was found in 62.9% (412 of 655) of gastrectomies with IC and in 33.3% (160 of 481) of those with DC. The numbers of specimens with EIM were significantly higher in the Pacific than in the Atlantic basin for both carcinoma phenotypes, particularly among elderly patients (>or=60 years). CONCLUSIONS: The proportion of gastrectomies with EIM was higher among populations at a higher gastric cancer risk than in those with a lower cancer risk. EIM was mostly associated with IC rather than DC or with miscellaneous gastric diseases (841 control gastrectomies) in both basins. The proportion of gastrectomies with EIM was significantly higher in Vancouver than in New York and in Santiago de Chile than in Buenos Aires, even though these populations reside at approximately the same geographical latitude, but in different basins. Environmental factors seem to accelerate the evolution of EIM.

Gastric ciliated metaplasia. A study of 3406 gastrectomy specimens from dwellers of the Atlantic and the Pacific basins.

BACKGROUND: Ciliated cells in gastrectomies from patients dwelling in the Pacific and Atlantic basins have been reported previously. AIM: To compare all the results in an attempt to explain the findings. METHODS: Sections from 3406 gastrectomies were reviewed: 1966 and 1440 from the Atlantic and Pacific basins, respectively. Ciliated cells and intestinal metaplasia (IM) were recorded; IM was classified into focal or extensive IM. The total number of sections/gastrectomy was noted. RESULTS: In the Atlantic basin, 5% of specimens had ciliated metaplasia (CM); it was more frequent in intestinal carcinoma (IC; 9%) than diffuse carcinoma (DC; 3%) or miscellaneous gastric diseases (MGD; 3%). In the Pacific basin, the frequency of specimens with CM was 29%: it was more frequent in IC (43%) than in DC (16%) or MGD (10%). The difference between the frequency of CM in specimens with IC or with DC/MGD in the Atlantic and the Pacific basins was significant (p < or = 0.05). The presence of CM was influenced by age and the extent of IM in both basins, but not by sex or the number of sections investigated. CONCLUSIONS: CM-apparently an independent microscopic marker-was significantly higher in the Pacific than in the Atlantic basin. Environmental carcinogens involved in the evolution of IM and IC seem to be implicated in gastric ciliogenesis. Carcinogens that differ in nature and/or in strength in both basins might activate the latent natural genes encoding ciliated processes in gastric cells in patients subsequently developing gastric carcinoma, more notably of intestinal type.

Gastric glassy cells: a study of 3202 gastrectomy specimens from dwellers of the Atlantic and Pacific basins.

Fifteen years ago we detected gastric cells with glassy cytoplasm (GCs) in the human pyloric antrum. The frequency of these cells was subsequently investigated in sections from gastrectomies carried on in populations dwelling on the rim of the Atlantic and Pacific basins. In this work we compared the results obtained in these disparate geographic regions. We reviewed sections from 3203 gastrectomies (1942 in the Atlantic basin and 1261 in the Pacific basin). In the Atlantic basin 12/1942 (0.6%) of the gastrectomies had GCs, whereas in the Pacific basin 26/1261 (2.1%) of the gastrectomies had GCs. The difference was significant (p<0.05). The proportion of gastrectomies with GCs was higher in patients in Vancouver, Canada, than in New York, and higher in Santiago de Chile than in Buenos Aires, despite the fact that these populations reside at approximately the same geographic latitude. Previous studies with the same material indicated that both the extension of intestinal metaplasia and the frequency of ciliated metaplasia were significantly higher in the Pacific than in the Atlantic basin. Hence, the difference in the frequencies of GCs appears to be a new indication that dissimilar environmental exposures in the two basins might have influenced the histological make-up of the gastric mucosa.

Quantitative determination of paclitaxel in human plasma using semi-automated liquid-liquid extraction in conjunction with liquid chromatography/tandem mass spectrometry.

This paper describes a high-throughput sample preparation procedure combined with LC-MS/MS analysis to measure paclitaxel in human plasma. Paclitaxel and an internal standard were extracted from plasma by a semi-automated robotic method using liquid-liquid extraction. Thereafter compounds were separated on a RP C18 column. Detection was by a PE Sciex API 3000 mass spectrometer equipped with a TurboIonSpray interface. The compounds were detected in positive ion mode using the mass transition m/z 854.6-->286.2 and m/z 831.6-->263.2 for paclitaxel and the internal standard, respectively. The limit of quantitation for paclitaxel was 1 ng/ml with an imprecision of 5.2% following extraction of 0.1 ml of plasma. Linearity was confirmed over the whole calibration range (1-1000 ng/ml) with correlation coefficients higher than 0.99 indicating good fits of the regression models. The inter and intra-day precision was better than 9.5% and the accuracy ranged from 90.3 to 104.4%. The assay was simple, fast, specific and exhibited excellent ruggedness.

The comparison of alcohol concentrations in postmortem fluids and tissues.

Fluid-tissue/blood alcohol ratios were calculated for a number of cases. The use of such factors to determine the blood alcohol concentration (BAC) becomes important when a blood specimen is not available or is contaminated. It was shown that estimates of blood alcohol concentrations derived from other physiological fluids or tissues can only be expressed as lying within a wide concentration range. Estimations of the BAC can be improved by using the stomach alcohol concentrations to determine if the decreased was in an absorption or postabsorption phase at the time of death.

Dissecting coronary artery aneurysm: a report of two cases.

Two cases of sudden, unexpected death resulting from coronary artery dissection have been reported. Since sudden and unexpected death falls within medical examiners' jurisdiction, the systematic autopsy examination of such cases offers an opportunity to evaluate this entity as well as other rare causes of natural death. A review of the literature concerning the subject has been presented.

[Oncologic post-resection reconstruction of mandibular defects]. / Ricostruzione post-resezione oncologica dei difetti della mandibola.

BACKGROUND AND AIM: If not reconstructed, mandibular defects resulting from oncological surgery can leave major functional and cosmetic sequelae which may impede these patients from returning to professional and family life. Reconstruction may be immediate or deferred, but the authors clearly recommend immediate reconstruction. METHODS: An analysis is made of the different techniques used for the reconstruction of mandibular defects, specifying those which are currently used and the situations in which they are applied. The advantages and disadvantages of microsurgical flaps and pedicled flaps are emphasised. The immediate use of endosseous implants is also discussed. RESULTS: The results of the various types of reconstruction are compared from a cosmetic and functional point of view. The latter includes a study of the quality of speech, deglutition, mastication and labial competence. Mastication is studied in two types of patients: those with osteointegrated implants with neomandibular reconstruction and those in whom osteointegrated implants were not used. All these patients survived 5 years after surgery. CONCLUSIONS: The authors recommend the immediate reconstruction of mandibular defects. Microsurgical flaps and pedicled flaps can be used for this purpose. Bone flaps may be used for endosseous titanium implants, whereas osseous flaps which do not provide a sufficient guarantee of rehabilitation should not be used. Implants should be inserted during oncological surgery, since postoperative radiotherapy may alter osteointegration of titanium implants are then used. The overall survival of these patients depends on the margins of local resection which are much wider using these techniques.

Diffuse acute cellulitis with severe neurological sequelae. A clinical case.

The incidence of head and neck odontogenic infections considerably diminished in the last decades due to appropriate antibiotic therapy. Herein we describe a case of acute diffuse facial cellulitis following tooth extraction in a patient with no apparent risk factor. During the acute process, injury was caused to the hypoglossal, vagal, glossopharyngeal and recurrent nerves of both sides. For this reason the patient currently has a nasogastric line for enteral feedings and a tracheotomy tube, which significantly affects his quality of life.

Papillary carcinoma of the base of the tongue. Case clinic.

Ectopic lingual thyroid tissue is an uncommon developmental anomaly. Tumours of identical pathological characteristics as those arising in the eutropic thyroid tissue, may be present in ectopic locations. There are very few cases of malignant tumours reported in the literature. Here we report a review of this pathology and we describe a case of a papillary carcinoma of the base of the tongue, located in ectopic lingual thyroid tissue, in a 66 year-old white man, complaining of dysphagia and oral bleeding. Surgical treatment was carried out, consisting of radical resection of the right hemineck, tumour resection, right hemiglossectomy and total thyroidectomy. Postoperative treatment with 131I and substitutive thyroid hormonal therapy was prescribed.

[Differential diagnosis of ulcerated gastric lesions]. / Diagnóstico diferencial de las lesiones gástricas ulceradas.

The semiological characteristics of the ulcerated gastric lesions, benign and malignant, are on study. Its frequency and location is analysed in 32,829 subjects of 40 or more years of age, apparently in good health, finding gastric ulcers in 2.98% been unique in 2.3% and multiple in 0.68%. A symptomatic group of 8,765 people of 40 or more years, showed gastric ulcer in 7.11% been unique in 5.18% and multiple in 1.93%. It is also reported the frequency of gastric cancer in both studied groups, which leads to permanently propose the differential diagnostic with benign lesions, underlying by its frequency those of ulcerated type. The value of the gastric biopsy in differential diagnosis represents finally an aid of major importance because its high yield.

[Bone scintigraphy in Erdheim-Chester disease]. / Gammagrafía ósea en la enfermedad de Erdheim-Chester.

Erdheim-Chester disease (ECD) is a rare disorder with fewer than 80 cases reported in the world. It consists of a non-Langerhans' cell histiocytosis that usually presents as pain due to bone involvement; however, the prognosis is marked by extraskeletal involvement. Although the final diagnosis needs an anatomophatologic study (normally through a bone biopsy), radiologic and scintigraphic findings are quasi pathognomonic. In this work, we report 2 ECD cases and their respective bone scans showing typical findings described in the literature. We found bilateral and symmetrical increased uptake of diaphyses and metaphyses of long bones, mainly in lower limbs. The mid-diaphyses and the epiphyses (partially in the first case) as well as the axial skeleton are spared.

[Endoscopic mucosectomy in incipient gastric malignant lesions]. / Mucosectomía endoscópica en lesiones gástricas malignas incipientes.

BACKGROUND: Endoscopic mucosectomy is a routine treatment mode for benign and malignant gastric lesions. The prognosis of patients with endoscopically treated early gastric cancer does not differ from patients subjected to surgical gastrectomy, when the indications for endoscopic mucosectomy are respected. AIM: To report the experience in endoscopic mucosectomy for early gastric cancer. PATIENTS AND METHODS: Between 1990 and 1997, 12 lesions in 10 patients, aged 48 to 107 years old, were treated with endoscopic mucosectomy. Clients were followed for 1 to 72 months after the procedure. RESULTS: Treated lesions ranged in size from 7 to 20 mm. Ten patients had differentiated carcinomas, one had an undifferentiated carcinoma and one had a primary gastric carcinoid. Endoscopic appearance was II a in six lesions, II c + II a in two, II a + II c in one. II c in one, I in one and II c + III in one. In two patients, the tumor persisted and were subjected to oncologic surgery. In one of these no malignant lesion was recognized in the pathological specimen. The other patient had a multicentric carcinoma that was already detected by endoscopy. Neither had lymph node metastases. Endoscopical and pathological follow up in the other 8 patients has not shown persistence or reappearance of malignant lesions during a follow up ranging from 3 to 72 months. CONCLUSIONS: Endoscopic mucosectomy can be a valuable therapeutic alternative in early gastric cancer.

[Early stomach cancer: the experience of the Hospital John Kennedy in Valdivia. 1976-1989]. / Cáncer gástrico incipiente: experiencia del Hospital John Kennedy en Valdivia. Periodo 1976-1989.

We report our experience with 19 patients with early gastric cancer in Valdivia, a southern province of Chile. All patients had symptoms and 15 had a preoperative biopsy. A mean of 39 days elapsed between biopsy and surgery. An emergency operation was performed in 3 patients. The mean lesion size was 10 cm2. An intramucous location was present in 9 patients and a submucous one in 10. Infiltration of the first lymph node barrier was observed in only 1 patient. A type P.1 resection was performed in 68% of patients, a type 2 resection in 11% and a type 3 in 5%. Recurrences were observed in 3 patients and 2 of them died. 5 year survival rate was 100% and 7 year survival was 68%.