Effectiveness of HPV vaccination in women reaching screening age in Italy.

BACKGROUND AND OBJECTIVES: A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. STUDY DESIGN: During 2010-2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. RESULTS: Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p=0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p<0.01 and 2.1% vs 6.5%, p=0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p<0.01 and 0.6% vs 6.7%, p-value<0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p<0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. CONCLUSIONS: Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.

Effects of drinking water and total sodium intake on blood pressure.

A cohort of 295 persons from a rural area of Michigan were studied to determine if a relationship exists between high levels of sodium in drinking water and blood pressure. Sodium in drinking water, dietary sodium intake, blood pressure, sodium excretion, height, and weight were measured. No significant relationships between daily mean sodium dietary intake, drinking water sodium, or sodium index (amount of drinking water sodium related to diet sodium intake), and mean blood pressure levels were found. A statistically significant relationship was found between 24-h urine sodium excretion and mean blood pressure for adults age greater than or equal to 18 yr (r = 0.239) and children age less than 18 yr (r = 0.359) and dietary intake and mean diastolic blood pressure in children only (r = 0.471). Furthermore, levels of sodium in drinking water were not related to blood pressure levels or presence of hypertension.

The diagnostic yield of histologic examination of seborrheic keratoses.

OBJECTIVE: To examine the diagnostic yield in submitting clinically diagnosed seborrheic keratoses for routine microscopic examination. DESIGN: Retrospective examination of preoperative and postoperative diagnoses based on information provided by the clinician on the laboratory worksheet and the subsequent histopathologic diagnosis. SETTING: A regional nonhospital-based dermatopathology laboratory with specimens submitted by physicians (dermatologists and nondermatologists) practicing in a 4-state midwestern region of the United States. PATIENT MATERIAL: A total of 5592 cutaneous pathology reports were reviewed. Specimens submitted with a preoperative clinical diagnosis of seborrheic keratosis, with or without a modifier, were examined. A comparison group with the clinical diagnosis of melanocytic nevus was reviewed. MAIN OUTCOME MEASUREMENT: Preoperative clinical diagnoses were compared with the microscopic diagnoses. RESULTS: Of 577 specimens clinically diagnosed and submitted as seborrheic keratoses, 37 (6.4%) were histologically diagnosed as malignant tumors. The rate of malignant tumors increased when clinical information suggested findings beyond the classic clinical presentation, such as irritation, or when a malignant tumor was considered in the differential diagnosis. Two lesions that histologically proved to be melanomas were in this group. Comparison of the seborrheic keratosis group with the nevus group showed that seborrheic keratoses were more likely to be malignant tumors than were melanocytic nevi. Clinically diagnosed seborrheic keratoses submitted by dermatologists were more likely than clinically diagnosed melanocytic nevi to be melanomas. CONCLUSIONS: Our data suggest that there were differences in the rate of malignant tumors between dermatologists and nondermatologists and that clinically diagnosed, surgically removed seborrheic keratoses are more likely than clinically diagnosed, surgically removed melanocytic nevi to be malignant tumors.

Reliability testing of the dermatology index of disease severity (DIDS). An index for staging the severity of cutaneous inflammatory disease.

OBJECTIVES: To describe a new severity of illness index for inflammatory skin disease called the Dermatology Index of Disease Severity (DIDS), and to show its preliminary use and reliability in staging disease in patients with psoriasis and dermatitis. DESIGN: Interobserver rating study using the DIDS with as many as 10 observers independently rating the same patient at a single point in time. SETTING: Ambulatory care clinics at an academic medical center with patients from various socioeconomic backgrounds. PATIENTS: Thirty-four patients with psoriasis and 15 patients with dermatitis were included in the study. MAIN OUTCOME MEASURES: The severity of illness for each patient was rated as 1 of 5 stages: 0, no evidence of clinical disease; I, limited disease; II, mild disease; III, moderate disease; and IV, severe disease. The degree of interobserver concordance was measured by the Cohen kappa statistic. RESULTS: All 5 stages were represented in the study of patients with psoriasis. The overall kappa statistic was 0.76, which is defined as substantial interobserver concordance. The use of the instrument in dermatitis showed good consensus in staging, where the kappa statistic was 0.41. CONCLUSION: We introduce an easy and efficient instrument for staging the severity of illness in inflammatory cutaneous diseases. The reliability of the DIDS is demonstrated in patients with psoriasis and in patients with dermatitis.

Protein synthesis after experimental injury in pigs. A comparison of infusion solutions with different amino acid patterns.

This study compared the effect of three amino acid solutions on protein metabolism after injury by measuring plasma amino acid pattern, nitrogen balance, total body protein synthesis and utilisation of administered nitrogen in an experimental protocol using pigs. Protein synthesis and nitrogen utilisation were determined using a 15N-tracer technique with recourse to mathematical model concepts. Control animals which had not undergone surgery had a lower urinary nitrogen excretion, a more favourable nitrogen balance, greater total body protein synthesis and utilisation of the infused amino acids during the infusion of an amino acid solution with a standard pattern of amino acids (A) than the operated animals infused with either solution A or two other test amino acid solutions B and C. Comparison of the post-operative data showed that if solution A is compared with solution (B) whose amino acid content takes account of changes in plasma amino acids following trauma and a solution (C) which contains a high fraction of branched chain amino acids, solution (B) yields the best results in respect of total body protein synthesis and nitrogen utilisation.

Microcirculation in hyperglycemic patients with IDDM without diabetic complications--effect of low-dose angiotensin-converting enzyme inhibition.

In patients with insulin-dependent diabetes mellitus (IDDM) angiotensin-converting enzyme inhibitors (ACEI) have been demonstrated to have beneficial effects in the secondary prevention of microvascular complications. There are only few data available regarding the effect of ACEI on microcirculation in patients with IDDM without any microvascular complications. In addition, there is little knowledge about ACEI action during acute hyperglycemia. In a pilot study nine patients with IDDM without any clinical signs of diabetic complications (5 females, 4 males, aged 33.3 +/- 1.0 years, duration of diabetes 11.4 +/- 3.0 years, HbA1 7.2 +/- 0.2% [normal range 4.8-7.4%], BMI 21.4 +/- 0.5 [kg/m2]) received 1.25 mg of the ACEI ramipril (Delix, Hoechst Marion Roussel, Frankfurt) over 4 weeks. Nine healthy volunteers (4 females, 5 males, age 27.4 +/- 1.1 years, HbA1 5.9 +/- 0.2% (p < 0.01 vs patients), BMI 22.2 +/- 0.9 [kg/m2]) served as controls. Using nailfold capillaroscopy we determined capillary blood cell velocity (CapiFlow, Lawrenz Electronics, Sulzbach, Germany) before and during post-occlusive hyperemia (200 mmHg for 3 minutes) as a provocative test. Before and after treatment patients were studied during hyperglycemia (blood glucose 250-350 mg/dl). Treatment with low-dose ramipril resulted in a significant decrease in the time to peak capillary blood cell velocity during post-occlusive hyperemia (17.8 +/- 7.7 vs 57.4 +/- 12.8 s, p < 0.01) in hyperglycemic patients. This effect was absent in healthy volunteers. Hemodynamic and metabolic parameters remained unchanged throughout the study in both groups. These data demonstrate that low-dose therapy with the ACEI ramipril is able to improve microcirculation in hyperglycemic patients with type 1 diabetes mellitus also before microvascular complications are evident. Prospective studies are necessary to evaluate whether this effect might be clinically relevant in the primary prevention of diabetic microangiopathy.

Dietary exposures to mineral hydrocarbons from food-use applications in the United States.

Food-use applications of mineral hydrocarbons (MHC) derived from petroleum sources result in dietary exposure to these compounds by consumers. Food applications of MHC, including white mineral oils, paraffin waxes, microcrystalline waxes and petrolatum, include both direct-additive uses in which the MHC is intentionally applied to the food and indirect-additive uses in which the MHC become components of the food due to migration from food-contact surfaces. A key consideration in evaluating the safety of these uses of MHC is the level of exposure that results. We estimated exposures to MHC in the US from food applications based primarily on a food-consumption approach, in which MHC concentrations in foods were multiplied by the amount of these foods consumed. This was a conservative estimate, because it assumes that all foods that might contain MHC in fact do so at maximum possible concentrations. A "poundage approach", in which the amount of MHC used in food applications was divided by the US population to determine maximum potential per capita exposures, was used to validate the consumption-based estimates. Exposures to MHC from food-packaging applications were estimated using the FDA's food-factor approach, which takes into account the volume and kinds of food packaged with specific types of materials. A conservative estimate of mean exposure to all MHC types combined is 0.875 mg/kg BW/day. Half of this, 0.427 mg/kg BW/day, is white mineral oils used as pan-release lubricants in baking, for de-dusting of stored grain, in confectioneries, and in coatings for fruits and vegetables. Nearly all of the remainder, 0.404 mg/kg BW/day, is petrolatum, primarily from its use as trough grease in bakery applications. Exposure to paraffin and microcrystalline waxes combined is only 0.044 mg/kg BW/day.

[Radiological aspects of esophageal intramural diverticulosis]. / Radiologische Aspekte der intramuralen Osophagusdivertikulose

The 9th observation of esophageal intramural diverticulosis is reported. The findings are compared with those of former publications. Clinically dysphagia is a leading symptom. Suction biopsy proved diverticulosis being the correct interpretation for radiological findings. The etiology is discussed. The change between symptom-free intervals with diverticulosis only and episods of dysphagia by secondary inflammation (reflux esophagitis, moniliasis, stenosis) stresses the importance of such secondary complications. These inflammations can hide the real diagnosis for a long time. The radiological findings are the key for diagnosis, however, they can be very small for years. During this period a diagnosis can only be achieved by knowledge of the disease and the skilful search for early symptoms.

[New therapeutic possibilities in the diagnosis of congenital cystic bile duct dilatations (author's transl)]. / Zur Diagnostik kongenitaler zystischer Gallengangsdilatationen im Zusammenhang mit neuen therapeutischen Möglichkeiten

The case of a 30-year-old woman with intra- and extrahepatic biliary dilatations (Caroli's disease) is reported. The features of the disease and its differential diagnosis are discussed. Special reference is given to the diagnostic approach by endoscopic retrograde cholangiography and to treatment with Chenodeoxy-cholicacid.

[Erroneous diagnoses in the retrograde demonstration of the biliary and pancreatic ducts. Results of a prospective study involving 197 examinations (author's transl)]. / Fehldiagnosen retrograder Gallen- und Pankreasgangdarstellungen--Erfahrungen einer prospektiven Studie von 197 Untersuchungen.

The results of endoscopic retrograde cholangio-pancreatography were evaluated in a prospective study of 126 patients in respect of diagnostic accuracy, as compared with surgery and clinical follow-up. The diagnosis was incorrect in 11 patients; in seven it failed to differentiate between acute and chronic pancreatitis. The discrepancies in the other four patients are described in detail, particularly with reference to prepapillary filling defects. The indications, advantages and limitations of ERCP are discussed.

Evaluation of erectile dysfunction with the sympathetic skin response in comparison to bulbocavernosus reflex and somatosensory evoked potentials of the pudendal nerve.

Sympathetic skin response (SSR) was investigated in 60 normal subjects (mean age 37.7 +/- 15.9) and 30 patients (mean age 47.2 +/- 12.0) referred from the department of urology for further electrophysiological evaluation of erectile dysfunction (ED). SSR was present in all normal subjects. Mean latency in the lower extremities was 2.16 +/- 0.20 sec. The coefficient of variance for repeated measurements in individual subjects was 10%. The latencies correlated slightly positively with the height of the subjects (r = 0.271, p < 0.05), but not with age. SSR in patients was compared to the bulbocavernosus reflex (BCR) and somatosensory evoked potentials (SSEP) of the pudendal nerve. All patients had a complete urological work-up with evaluation of hormonal function, pharmacotesting and Dopplersonography, as well as pharmacocavernosography and measurement of nocturnal penile tumescence if indicated. Six patients were diagnosed to have functional impotence, 4 dysfunctions were probably of vascular origin, 5 were neurogenic and 15 of the mixed type of vascular and neurogenic origin. Diabetes mellitus was the underlying disease in 14. In the two groups with neurogenic involvement (5 neurogen, 15 mixed) 14 of 20 patients had a pathological BCR, 12 had pathological SSEP and 9 had an absent SSR. Of these 9 patients two showed normal BCR and SSEP. Sensitivity for neurogenic dysfunction was 70% for the BCR, 60% for the BCR and SSEP, but that it detects some patients with erectile dysfunction, in whom other parameters are not pathological.(ABSTRACT TRUNCATED AT 250 WORDS)

[Laparoscopic cholecystectomy as standard intervention in symptomatic cholecystolithiasis. Experiences with 1,277 patients]. / Die laparoskopische Cholecystektomie als Standardeingriff bei symptomatischer Cholecystolithiasis. Erfahrungen bei 1277 Patienten.

As a result of 1277 laparoscopic cholecystectomies, which were performed as a standard procedure in uncomplicated and complicated symptomatic cholecystolithiasis, the complication-rates of conventional cholecystectomy and laparoscopic cholecystectomy are compared. It can be demonstrated, that the adoption of the principles of conventional cholecystectomy into laparoscopic technique and a careful preparation can reach the same high level of safety as the so called "gold-standard".

Pitfalls in the diagnosis of new-onset frontal lobe seizures.

We reported the case of a young woman who received an antiepileptic drug after a first possible generalized tonic-clonic seizure with no clear inter-ictal epileptic paroxysms in the routine electroencephalogram. Her stereotypical movements decreased but did not disappear with treatment. Then a diagnosis of PNES was considered by neurologist after witnessing a stereotypical motor episode. While AED treatment was decreased and stopped, epileptic seizure frequency and severity increased with secondary generalized tonic-clonic seizures. Then she presented postictal psychotic features that combined with video-EEG findings led to the final diagnosis of new onset pre-frontal lobe epilepsy.

Determination of renal tissue ibandronate levels in rats with normal and mildly impaired renal function.

BACKGROUND: After entering the blood, bisphosphonates are immediately bound to bone or excreted unchanged by the kidney. During renal excretion about 0.5% of administrated dosage remains in kidney tissue. The renal tissue level of bisphosphonates (RTL) decreases over time and remains at about 0.15% after 3weeks, but the influence of renal insufficiency (RI) is unclear. METHOD: We investigated the influence of mild to moderate RI on RTL of ibandronate (IBD). First a method for determination of RTL was implemented and validated. We measured RTL in rats with normal renal function (SHAM) and after unilateral nephrectomy (UNX). In each case one SHAM and one UNX groups received one or alternatively 9 times every 3weeks a dosage of 1.5mg/kg IBD. After the last dosage the rats were sacrificed and RTL of IBD were determined. RESULTS: In SHAM-rats IBD concentrations increased from 272.7ng/g kidney after one injection to 428.9ng/g kidney after nine injections (p<0.0001). RTL in UNX rats likewise increased significantly (p<0.0001) from 289.9ng/g kidney to 520.2ng/g kidney. CONCLUSION: Our study found a 1.6 fold increase of RTL in SHAM rats and a 1.8 fold increase of RTL in UNX rats after nine versus one injection. As steady state is generally reached after five half-lives we anticipate no further accumulation on continued treatment.

Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to a number of agents than other rat strains and the results of this study suggest that this may contribute, along with pharmacokinetic differences, to the inflammatory response of F-344 rats to dietary MHCs.