Complete Genome Sequence of the Human Herpesvirus 6A Strain AJ from Africa Resembles Strain GS from North America.

The genome sequence of human herpesvirus 6A (HHV-6A) strain AJ was determined in a comparison of target enrichment and long-range PCR using next-generation sequencing methodologies. The analyses show 85 predicted open reading frames (ORFs), conservation with sequenced HHV-6A reference strain U1102, and closest identity to the recently determined GS strain, despite different geographic origins (United States and Gambia).

Analyses of germline, chromosomally integrated human herpesvirus 6A and B genomes indicate emergent infection and new inflammatory mediators.

Human herpesvirus-6A (HHV-6A) is rarer than HHV-6B in many infant populations. However, they are similarly prevalent as germline, chromosomally integrated genomes (ciHHV-6A/B). This integrated form affects 0.1-1 % of the human population, where potentially virus gene expression could be in every cell, although virus relationships and health effects are not clear. In a Czech/German patient cohort ciHHV-6A was more common and diverse than ciHHV-6B. Quantitative PCR, nucleotide sequencing and telomeric integration site amplification characterized ciHHV-6 in 44 German myocarditis/cardiomyopathy and Czech malignancy/inflammatory disease (MI) patients plus donors. Comparisons were made to sequences from global virus reference strains, and blood DNA from childhood-infections from Zambia (HHV-6A mainly) and Japan (HHV-6B). The MI cohort were 86 % (18/21) ciHHV-6A, the cardiac cohort 65 % (13/20) ciHHV-6B, suggesting different disease links. Reactivation was supported by findings of 1) recombination between ciHHV-6A and HHV-6B genes in 20 % (4/21) of the MI cohort; 2) expression in a patient subset, of early/late transcripts from the inflammatory mediator genes chemokine receptor U51 and chemokine U83, both identical to ciHHV-6A DNA sequences; and 3) superinfection shown by deep sequencing identifying minor virus-variants only in ciHHV-6A, which expressed transcripts, indicating virus infection reactivates latent ciHHV-6A. Half the MI cohort had more than two copies per cell, median 5.2, indicative of reactivation. Remarkably, the integrated genomes encoded the secreted-active form of virus chemokines, rare in virus from childhood-infections. This shows integrated virus genomes can contribute new human genes with links to inflammatory pathology and supports ciHHV-6A reactivation as a source for emergent infection.

[Changes in therapy aims and palliative treatment for severe stroke]. / Therapiezieländerung und Palliativmedizin beim schweren Schlaganfall.

Recent years have seen considerable advances in acute stroke treatment. Patients who survive the acute phase following major stroke often retain severe limitations of motor, cognitive, and communicative functions. In such patients whose death is imminent, curative therapies should be avoided. Instead, the goal of any therapy should shift to palliative treatment and concentrate on reducing causes of suffering. Palliative methodologies and concepts are already well established in neurology, e.g. for amytrophic lateral sclerosis. Particularly those stroke patients who remain stable for a long period with massive neurological deficits require interdisciplinary palliative care that goes beyond mere reduction of symptoms and seeks a response to possible complications and the question of maintaining life-preserving measures. Not only medical indications but also the expressed or presumed will of the patient must be included in such considerations. This article describes and elucidates basic questions of palliative medicine and symptomatic palliative treatment concepts for stroke patients.

A prospective evaluation of occult disorders in obstructed defecation using the 'iceberg diagram'.

OBJECTIVE: Surgical treatment of constipation and obstructed defecation (OD) carries frequent recurrences, as OD is an 'iceberg syndrome' characterized by 'underwater rocks' or occult diseases which may affect the outcome of surgery. The aim of this study was to evaluate occult disorders, in order to alert the clinician of these and minimize failures. METHOD: One hundred consecutive constipated patients with OD symptoms, 81 women, median age 52 years, underwent perineal examination, proctoscopy, anorectal manometry and anal/vaginal ultrasound (US). Anorectal physiology and imaging tests were also carried out when indicated, as well as psychological and urogynaecological consultations. Symptoms were graded using a modified 1-20 constipation score. Both evident (e.g. rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using a novel 'iceberg diagram'. The type of treatment, whether conservative or surgical, was also recorded. RESULTS: Fifty-four (54%) patients had both mucosal prolapse and rectocele. All patients had at least two occult OD-related diseases, 66 patients had at least three of them: anxiety-depression, anismus and rectal hyposensation were the most frequent (66%, 44% and 33%, respectively). The median constipation score was 11 (range 2-20), the median number of 'occult disorders' was 5 (range 2-8). Conservative treatment was carried out in most cases. Surgery was carried out in 14 (14%) patients. CONCLUSION: The novel 'iceberg diagram' allowed the adequate evaluation of OD-related occult diseases and better selection of patients for treatment. Most were managed conservatively, and only a minority were treated by surgery.

A prospective evaluation of occult disorders in obstructed defecation using the 'iceberg diagram'.

OBJECTIVE: Surgical treatment of constipation and obstructed defecation (OD) carries frequent recurrences, as OD is an 'iceberg syndrome' characterized by 'underwater rocks' or occult diseases which may affect the outcome of surgery. The aim of this study was to evaluate occult disorders in order to alert the clinician of these and minimize failures. METHOD: One hundred consecutive constipated patients with OD symptoms, 81 female patients, median age 52 years, underwent perineal examination, proctoscopy, anorectal manometry, and anal/vaginal ultrasound. Anorectal physiology and imaging tests were also carried out when indicated, as well as psychological and urogynaecological consultation. Symptoms were graded using a modified 1-20 constipation score. Both evident (e.g. rectocele) and occult (e.g. anismus) diseases were prospectively evaluated using a novel 'iceberg diagram'. The type of treatment, whether conservative or surgical, was also recorded. RESULTS: Fifty-four (54%) patients had both mucosal prolapse and rectocele. All patients had at least two occult OD-related diseases, 66 patients had at least three: anxiety-depression, anismus and rectal hyposensation were the most frequent (66%, 44% and 33% respectively). The median constipation score was 11 (range 2-20), the median number of 'occult disorders' was 5 (range 2-8). Conservative treatment was carried out in most patients. Surgery was carried out in 14 (14%) patients. CONCLUSION: The novel 'iceberg diagram' allowed the adequate evaluation of OD-related occult diseases and better selection of patients for treatment. Most were managed conservatively, and only a minority were treated by surgery.

The rectal pocket syndrome after stapled mucosectomy.

OBJECTIVE: Stapled rectal mucosectomy (SM) is less painful than manual haemorrhoidectomy but may be followed by unusual complications which may require reinterventions. The aim of the present study was to report on a particular postoperative complication, the rectal pocket syndrome (RPS). METHODS: Six patients, four females and two males, five with severe proctalgia and signs of intermittent sepsis and one with faecal soiling following SM, underwent clinical examination, proctoscopy (n = 5) anal manometry and ultrasound (n = 4) revealing a painful rectal intramucosal pocket with an endoluminal orifice at the level of the suture line. Four of them underwent a reintervention. RESULTS: At surgery, a faecolyth was found to be entrapped in the rectal pocket with an underlying chronic abscess in four patients. The cavity was laid open and curetted in all cases. One of the females needed a fistulotomy of a low intersphincteric track after one year. In none of the others did endorectal pocketing and abscess or prostatitis recur after a mean follow up of 25 months (range 2-60 months). The male patient still had moderate postevacuation pain and prostatitis possibly via a bacterial translocation after two months. Overall, the incidence of the post mucosectomy RPS at our Units was 2.5%. CONCLUSIONS: The RPS can occur after SM, is likely to be due to a failure of either the purse-string or of the staples causing a suture defect leading to an intramural sinus, and may be successfully treated by a transanal lay-open in most cases.

An evidence-based treatment algorithm for anal fissure.

Guidelines for the treatment of anal fissure have been published in the USA and UK but differ. Many centers follow guidelines based on local experience. In December 2005, we met with the aim of developing an evidence-based treatment algorithm for anal fissure, applicable to both primary and secondary care. This algorithm may rationalize the treatment of anal fissure in primary and secondary care settings.

Mesh crural repair of large paraesophageal hiatal hernias.

Surgical repair is indicated in patients with paraesophageal hernias but is associated with a high recurrence rate. Our objective was to assess the safety and efficacy of mesh reinforcement of the crural closure in laparoscopic paraesophageal hernia repair. We conducted a 7-year retrospective review of all patients undergoing laparoscopic paraesophageal hernia repair with or without use of mesh. The main outcome measures were use of mesh, reason for use, age, sex, preoperative symptoms, length of operation, length of hospital stay, postoperative complications, and long-term follow-up conducted by physician interview. Twelve patients were repaired with mesh (Group A) and 12 without (Group B). Age, sex, operating time, length of hospital stay, and postoperative complications were similar in both groups. In Group A two patients required an interposition graft and ten required mesh reinforcement of the crural closure. One Group A patient developed an early recurrence requiring a reoperation, and one Group B patient developed a gastric leak where the fundus was sutured to the crura. The remainder of the patients experienced resolution of their symptoms at 2 weeks follow-up. Long-term follow-up (average 37 months) showed one Group B patient with a recurrence of reflux symptoms, but an upper gastrointestinal study showed no recurrence of hernia. All others remained asymptomatic. We conclude that the use of mesh in laparoscopic repair of large paraesophageal hernias appears safe and may reduce recurrence.

The Chievitz juxtaparotid organ.

The Chievitz juxtaparotid organ represents a macroscopic longitudinal formation, which is developed from oral cavity ectoderm in its lateral wall. As to its function, the organ probably represents a mechanosensor with different qualities of perception. The information coming from its sensors takes part in different activities of the lateral wall of oral cavity during sucking, swallowing, mastication, speech, protecting reflexes and wall tonus. The Chievitz juxtaparotid organ is not only a morphologically interesting structure, but is of great importance also for clinic and surgical pathology of the oral cavity.

Thymectomy and multiple sclerosis: ultrastructural study of an experimental model.

Transmission electron microscopy was performed on specimens of the thymus of rats induced for acute experimental allergic encephalomyelitis (EAE). The ultrastructural alterations of the thymus were progressive and correlated with EAE development. The thymic disorganization was due to a progressive degeneration of both epithelial cells and thymocytes. These data suggest a direct involvement of the epithelial thymic cells and thymocytes in EAE pathogenesis and may suggest the intriguing therapeutic concept of thymectomy in the management of multiple sclerosis.

Interposition vein cuff in infrainguinal prosthetic bypasses.

The Authors describe the interposition vein cuff technique as an adjuvant method to infrainguinal prosthetic bypass grafts. The haemodynamic, mechanical and humoral factors thought to be involved in the beneficial effects of the vein cuff are herein discussed. The results of the main series suggest the use of this method particularly in patients without any available autologous vein conduit requiring a below-knee popliteal or crural reconstruction.

Adjuvant arteriovenous fistula in infrapopliteal bypasses.

The poor results obtained with the use of prosthesis in infrapopliteal arterial bypass grafting for critical limb ischaemia led to the introduction of several types of adjuvant arteriovenous fistula to improve the patency and limb salvage rates in patients who have no suitable autologous vein. The main aim of adjunctive arteriovenous fistula in infrageniculate prosthetic bypass is to accelerate the blood flow velocity through the prosthetic graft above the thrombotic threshold level. Since they are subject of great debate among vascular surgeons, the Authors have briefly reviewed the haemodynamic aspects and results reported with the use of such procedures.

[Parathyroidectomy: our school experience]. / La paratiroidectomia: esperienza di Scuola.

The Authors evaluated the results obtained in 145 patients operated on for hyperparathyroidism: 109 patients had primary hyperparathyroidism and 36 patients had secondary hyperparathyroidism. Preoperative localization by ultrasonography was assured in all cases, while only few patients were preoperatively evaluated by arteriography and selected venous sampling of the parathyroid hormone concentration. After surgical resection for primary hyperparathyroidism, transient postoperative hypoparathyroidism occurred in 30 patients (27.5%), recurrent disease occurred in 3 patients (2.7%), while 1 patient experienced persistent hypoparathyroidism (1%). In 3 patients (3%), resection of a solitary adenoma and biopsy of all parathyroid glands resulted in a permanent hypoparathyroidism which required long-term administration of vitamin D and oral calcium. Neither recurrent nor persistent hyperparathyroidism occurred in patients surgically treated for secondary hyperparathyroidism, and no postoperative hypoparathyroidism was registered. The Authors emphasize the importance of an adequate surgical strategy and accurate initial cervical exploration of the parathyroid glands as a necessary step for the correct treatment of this challenging disease.

[Surgery of differentiated cancer of the thyroid]. / La chirurgia del cancro differenziato della tiroide.

A retrospective study on patients with differentiated thyroid carcinoma operated on at the 3rd Department of General Surgery of the University "La Sapienza" of Rome from 1970 to 1996 was performed. In 709 patients total thyroidectomy was performed as the minimal procedure acceptable, while 19 patients had subtotal thyroidectomy out of necessity. A functional ipsilateral or bilateral lymphnectomy of the neck was performed in 256 cases. This wider operation is indicated in the presence of metastatic lymph nodes and on principle in patients older than forty-five years in which at least another risk factor is present. Long term follow-up (12 years) was assured in 302 patients and the survival rate was 92% independently from the histotype (papillary or follicular). The survival rate of a group of 120 patients (80 with papillary and 40 with follicular carcinoma) was analyzed in relation to the risk factors. This group analysis demonstrated a very low mortality rate in patients with low risk index and an increased rate in patients with a high risk index.

The immunolocalization of PGP 9.5 in normal human kidney and renal cell carcinoma.

The Authors studied the localization of protein gene product (PGP) 9.5-like immunoreactivity in normal human kidney tissue and compared the results with the same immunostaining in renal cell carcinoma. PGP 9.5-like immunoreactivity was found in cells of distal convoluted tubules and in some glomerular capillaries. The cells of proximal convoluted tubules did not show any immunostaining. Sections from renal cell carcinoma showed a very low immunostaining or were negative for PGP 9.5. As PGP 9.5 is a marker of the diffuse endocrine system, the Authors believe that the stained cells of distal tubules should be considered as neuroendocrine cells. The negative reaction to PGP 9.5 antibodies in renal cell carcinoma is rather surprising since not only tumours of neuroectodermal origin, but also tumours of other origin and tissues from some chronic degenerative diseases show a positive reaction. The explication of a negative reaction in renal cell carcinoma remains open: one of the possible explanations could be the specific histogenesis of this tumour.

Vascular anastomoses among abdominal organs in laboratory animals.

Vascular anastomoses among abdominal organs were studied in 289 laboratory mammals. Arterial anastomoses joining the wall or the parenchyma of the abdominal organs were studied in 108 animals and were found among the stomach, the spleen and the pancreas. In the cat, such anastomoses occur in 86.7% of cases, in the guinea pig in 73.3%, in the hedgehog in 61.1%, in the rabbit in 3.3%. The highest mean value was found in the cat: 3.1 anastomoses. Venous anastomoses were studied in 181 animals and were found among the stomach, the spleen and the pancreas, too. With the exception of the guinea pig (found in 89.1% of cases), these anastomoses were found almost in all cases of other five examined species. They mostly occur between the stomach and the spleen, and between the spleen and the pancreas with some differences in the guinea pig and the cat. The highest mean value was found in the rat: 6.1 anastomoses. For the present, it is not possible to state any significant differences among orders and species examined. As these vascular anastomoses occur also in man, we believe that they should be preserved during surgical procedures.