Bovine Papillomavirus: New Insights into an Old Disease

Bovine papillomaviruses (BPVs) are small DNA tumoral viruses able to induce benign cutaneous and/or mucosal epithelial lesions. Generally, the benign tumours affecting the skin or mucosa spontaneously regress, but under special circumstances, the defence system may be overwhelmed, thus leading to cancer, especially in the presence of immunosuppressant and mutagen agents from bracken fern. To date, thirteen different BPV genotypes have been associated with skin and mucosal tumours in cattle, and out of these, only four types (BPV‐1, ‐2, ‐5 and ‐13) cross‐infect other species. Recent investigations in vivo have revealed new insights into the epidemiology and pathogenesis of this viral infection. This review briefly discusses viral epidemiology, will give data on BPV genome structure and viral genes and will describe the cellular events and new aspects of both cutaneous and mucosal tumours in large ruminants. Finally, some aspects of active immunization will be described.     

Granulomatous Mastitis: A Spectrum of Disease

Summary

Background

Granulomatous disease within the breast can result from a variety of causes.

Patients and Methods

We present 3 cases of this condition with 3 different underlying diagnoses.

Results

Each case was initially labelled as idiopathic granulomatous mastitis, although this was proven not to be correct on further investigation.

Conclusion

Clearly, identifying the correct underlying diagnosis is essential in granulomatous breast lesions as the treatment varies widely depending on the underlying aetiology. Effective communication and feedback in the context of the multidisciplinary team are vital to the diagnostic process in such challenging cases.Key Words: Granulomatous mastitis, Breast     

African–Americans and Kidney Disease: New Insights into an Old Problem

Chronic kidney disease and end-stage renal disease are a growing epidemic, both in the United States and worldwide. African–Americans are disproportionately afflicted with kidney disease. The reasons for this disparity are multiple, but ultimately unclear. Not only are diabetes mellitus and hypertension more prevalent in African–Americans, but also end-organ damage from these processes appears also to be accelerated. Also, certain primary and secondary glomerular diseases are more prevalent and more severe in African–Americans than in Caucasians. Despite controlling for these factors and socioeconomic status, the increased prevalence of kidney disease in African–Americans is still not entirely explained. Recently, two studies identified certain alleles within the MYH9 gene locus that are more frequently expressed in African–Americans with focal segmental glomerulosclerosis and non-diabetic renal disease. These studies emphasize the important role that genetic factors may play in explaining racial discrepancies in kidney disease, and represent exciting areas for new research.     

Dialysis-Associated Hypoxemia: Insights into Pathophysiology and Prevention

It is clear that much research continues in an attempt to better understand DAH. A reasonable synthesis scenario based on current knowledge is as follows. Within the first 5–10 minutes of dialysis with a cellulosic membrane, blood contact leads to complement activation, generation of anaphylatoxins, leukoagglutination, and pulmonary microleukoaggregates. In addition, release of thromboxane in the lung occurs and causes pulmonary hypertension. This series of events causes mild hypoxemia and is preventable when noncellulosic membranes are used. As dialysis proceeds subsequent hypoxemia is dependent on the dialysate composition. With acetate dialysate, outward CO₂ dialysance occurs concomitant with inward acetate dialysance. This leads to reflex hypoventilation, increased oxygen consumption (which lowers RQ), and possibly direct central respiratory suppression. These changes account for the late hypoxemia seen. With bicarbonate dialysate, the above events do not occur. If rapid alkalinization ensues, however, because of a high dialysate bicarbonate concentration, hypoventilation and hypoxemia may be seen. A clear understanding of these pathophysiologic mechanisms provides a framework from which the preventative measures outlined can be understood and applied. Future research should focus on a better understanding of the sequence of events following blood-membrane interaction, particularly in regard to activation of prostenoids. In addition, a more precise method is needed to determine the appropriate bath bicarbonate concentration for individual patients to avoid rapid alkalinization and hypoxemia. Finally, methods of identification of patients at risk of serious consequences from DAH need to be developed as well as noninvasive means of monitoring such individuals during dialysis. Much progress has been made in these areas in the past 10 years, but there is still more to learn.     

Dialysis-Associated Hypoxemia: Insights into Pathophysiology and Prevention

It is clear that much research continues in an attempt to better understand DAH. A reasonable synthesis scenario based on current knowledge is as follows. Within the first 5–10 minutes of dialysis with a cellulosic membrane, blood contact leads to complement activation, generation of anaphylatoxins, leukoagglutination, and pulmonary microleukoaggregates. In addition, release of thromboxane in the lung occurs and causes pulmonary hypertension. This series of events causes mild hypoxemia and is preventable when noncellulosic membranes are used. As dialysis proceeds subsequent hypoxemia is dependent on the dialysate composition. With acetate dialysate, outward CO₂ dialysance occurs concomitant with inward acetate dialysance. This leads to reflex hypoventilation, increased oxygen consumption (which lowers RQ), and possibly direct central respiratory suppression. These changes account for the late hypoxemia seen. With bicarbonate dialysate, the above events do not occur. If rapid alkalinization ensues, however, because of a high dialysate bicarbonate concentration, hypoventilation and hypoxemia may be seen.
A clear understanding of these pathophysiologic mechanisms provides a framework from which the preventative measures outlined can be understood and applied. Future research should focus on a better understanding of the sequence of events following blood-membrane interaction, particularly in regard to activation of prostenoids. In addition, a more precise method is needed to determine the appropriate bath bicarbonate concentration for individual patients to avoid rapid alkalinization and hypoxemia. Finally, methods of identification of patients at risk of serious consequences from DAH need to be developed as well as noninvasive means of monitoring such individuals during dialysis. Much progress has been made in these areas in the past 10 years, but there is still more to learn.     

Stuttering Priapism: Insights into Pathogenesis and Management

Priapism is defined as a persistent, painful erection that continues beyond, or is unrelated to, sexual stimulation. It may be categorized as either ischemic (low/absent flow) or nonischemic (high flow). Stuttering priapism is a variant of the ischemic type that is characterized by repetitive, transient, painful, self-limiting episodes of priapism. It is associated with various hematological disorders, including sickle cell disease and pharmacological treatments. The consequences of ineffective treatment of priapism are erectile dysfunction and impaired quality of life due to chronic pain and physical disfigurement. Many of the existing medical therapeutic options for treatment of stuttering priapism are nonmechanistic and associated with significant adverse effects. However, the scientific knowledge of stuttering priapism has transitioned in the past few years, from a condition that is poorly understood to one that has borne a burst of evolving molecular science. In this review, the pathophysiology of priapism is discussed, with particular emphasis on new molecular effectors and mechanisms. Novel treatment methods, as well as potential future agents, based on the emerging molecular evidence are discussed.     

Idiopathic Granulomatous Mastitis: A Heterogeneous Disease with Variable Clinical Presentation

Introduction Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast disease that presents with variable local manifestations. We describe here the different management protocols based on the clinical presentation of these patients. Methods A retrospective review of 20 histopathologic confirmed cases of IGM seen over a period of 10 years was performed. Results The median age was 34 years (age range: 21–45 years). All were married, parous with history of breast feeding. Ill-defined mass mimicking carcinoma was the commonest presentation (70%); however, with the presence of signs of inflammation like pain (55%), redness (40%), and peau d’orange (40%), an inflammatory process appeared more likely. Axillary lymph node enlargement was infrequently seen (40%). Radiologic findings (mammography and ultrasound) were nonspecific. Histopathology showed the characteristic lobular distribution of granulomatous inflammation in all cases. Surgically, 7 patients had abscess drainage with open biopsy, and 7 patients had lumpectomy. Six patients with diffuse breast involvement were diagnosed by core needle biopsy only. Microbial cultures showed no growth. Antibiotics were given empirically when signs of inflammation where present. Two patients needed further abscess drainage followed by persistent sinus excision 3–6 weeks later. The median follow-up was 24 months (range: 15–42 months). Seventeen patients (85%) were recurrence-free, and 3 patients (15%) were lost to follow-up. Conclusions Management of IGM cases needs to be tailored according to the clinical presentation. Precise radiologic and pathologic data interpretation by a multidisciplinary breast team will facilitate diagnosis and minimize unnecessary intervention.     

Glomerular Deposition Diseases: Insights into Mechanisms

Recent experimental studies demonstrate that glomerular basement membrane immune deposits may be formed locally or by deposition of intact complexes from the circulation. Electrostatic interactions may play a role in both of these mechanisms and may account, at least in part, for differences in patterns of localization in the various deposition diseases.     

Insights into surgical trials: methodological challenges and solutions

Background

Novel surgical methods and procedures used to be introduced by experts and were established depending on the corresponding success that was noted. Surgical trials representing evidence level 1b were and still are called into question for different reasons. Prospective randomized controlled trials comparing various surgical strategies that were conducted over the past 11 years in the clinical trial unit in the department of general, visceral, and transplantation surgery of the University of Heidelberg pointed out problems as well as possible solutions for surgical trials’ characteristics.

Purpose

When planning a study within a department of surgery, several aspects have to be considered. The article aims at outlining pitfalls that have to be dealt with as well as possible solutions by outlining experiences within several conducted trials.

Conclusions

The compilation of solutions announcing the challenges of surgical studies shows that valid high-quality trials are feasible.     

Merkel Cell Carcinoma: Spontaneous Resolution and Management of Metastatic Disease

Background. Merkel cell carcinoma (MCC) is a rare, aggressive, cutaneous neoplasm. The primary form of initial treatment is wide surgical excision. The use of Mohs micrographic surgery as the primary form of treatment in MCC has been controversial. The course of MCC is often aggressive, with early metastasis, widespread disease, and death. Despite the poor prognosis, spontaneous regression has occasionally been reported.
Objective. We describe the clinical course of two patients with Merkel cell carcinoma who underwent treatment with Mohs micrographic surgery for the primary MCC. Metastases were excised in the first case and spontaneously regressed in the second. Both patients are without clinical disease at the time of this report.
Methods. Histopathology, clinical records, and the current literature are reviewed.
Results. One patients was without recurrence of MCC for 13 years of follow-up. The other patient experienced clinical spontaneous remission after nodal spread of the disease, with no recurrence for 18 months after clinical remission and 24 months after surgery.
Conclusion. The treatment of Merkel cell carcinoma with Mohs micrographic surgery (MMS) has been successful for the control of primary skin disease, and is at least comparable to wide excision. Spontaneous regression may occur in the course of this usually relentless and aggressive disease. The explanation for spontaneous regression of MCC is unknown.     

Immunopathology of an hDAF transgenic pig model liver xenotransplant into a primate

BACKGROUND: hDAF transgenic pigs do not display the inherent hyperacute rejection reactions of pig-to-primate xenotransplants. The purpose of this study was to determine the immunopathologic phenomena following an hDAF transgenic pig hepatic orthotopic xenotransplant into a baboon. METHODS: Donor animals were unmodified pigs (n=4) and hDAF transgenic pigs (n=2). Recipient animals were baboons (Papio anubis). Liver biopsies were immunostained using monoclonal antibodies to C3, C5b-9, IgG, IgM, CD2, CD4, CD8, CD68, CD20, Bric 216, CD31, and fibrin, and polyclonal antibody to C4. RESULTS: hDAF transgenic grafts showed IgG, IgM, and C4 endothelial deposits. However, no fibrin, C3, or C5b9 deposits were observed after reperfusion. hDAF xenografts displayed CD31 staining in the portal spaces, perilobular areas, and at hepatic sinuisoidal levels. The baboon that lived for 4 days displayed either CD4 or CD8 T-cells periportal infiltrate. CONCLUSIONS: Future studies will seek to determine the physiologic role of CD31 hepatic sinusoidal expression in transgenic xenotransplants, and will also study the role of T-cell infiltrates in xenograft rejection.     

Insights into causes of sexual ambiguity

Our understanding of the causes of sexual ambiguity has progressed from the determination of the hormonal etiologies to defining the genetic basis of intersex disorders. The localization of specific genes involved in the process of sexual differentiation has made it possible to determine the mutations and other molecular events that result in sexual ambiguity. With this information, some disorders can now be diagnosed before birth and possibly even treated in utero.     

Rapid Resolution of Nitrofurantoin-Induced Interstitial Lung Disease

We report the case of a 40-year-old woman diagnosed with interstitial lung disease due to long-term nitrofurantoin therapy. Despite severely distorted bronchiolar architecture and honeycombing confirmed by computed tomography of the thorax, transbronchial biopsy showed a pattern of acute/subacute interstitial pneumonitis and the symptoms and radiographic findings disappeared within 1 month after administration of prednisone. This case shows that nitrofurantoin-induced lung disease may run a benign course and respond favorably to corticosteroids, even when there is radiographic evidence of established lung fibrosis. Transbronchial biopsy might be useful for assessing the reversibility of pulmonary lesions associated with nitrofurantoin.