Colonic diverticular disease in patients 40 years old or younger.

Diverticular disease in patients 40 years of age or younger has been described as rare but virulent. Previous studies, based on age, on diverticular disease are often confusing because of inexact definitions of the disease status. With these criticisms in mind, the authors studied 322 clinical records on patients admitted with a diagnosis of colonic diverticulosis or diverticulitis to the University of New Mexico Hospital and the Lovelace Medical Center. Of these patients, 285 had documented evidence of colonic diverticula with only 6 per cent of these being 40 years of age or younger. The criteria for acute diverticulitis were met by 86 patients, 17 of whom were 40 years of age or younger. The younger group had disproportionately more men, particularly Hispanics. The authors conclude that acute diverticulitis is more common in the young than suggested by previous reports, but the behavior of the disease is not distinctive.     

Renal involvement in mitochondrial cytopathies

Mitochondrial cytopathies have long been regarded as neuromuscular diseases. However, an oxidative phosphorylation disorder may give rise to various symptoms in other organs or tissues which are dependent upon mitochondrial energy supply. A broad spectrum of clinical symptoms have been described in these patients, including renal symptoms. The most frequent is proximal tubular dysfunction with a more or less complete de Toni-Debré-Fanconi syndrome. A few patients have been reported with tubular acidosis, Bartter syndrome, chronic tubulointerstitial nephritis, or nephrotic syndrome. The diagnosis of a respiratory chain deficiency is difficult when only renal symptoms are present but should be easier when another seemingly unrelated symptom is observed. Metabolic screening for abnormal oxidoreduction status in plasma, including lactate/pyruvate and ketone body molar ratios, can help to identify patients for further investigations. These include the measurement of oxygen consumption by mitochondria, the assessment of mitochondrial respiratory enzyme activities by spectrophotometric studies, and when possible, the molecular analysis of mitochondrial DNA. Any mode of inheritance can be observed: sporadic, autosomal dominant or recessive, or maternal inheritance. No satisfactory therapy is presently available for mitochondrial disorders.     

Huntington's disease: pathological mechanisms and therapeutic strategies

Huntington's disease (HD) is a devastating neurodegenerative disorder that occurs in patients with a mutation in the huntingtin or IT15 gene. Patients are plagued by early cognitive signs, motor deficits, and psychiatric disturbances. Symptoms are attributed to cell death in the striatum and disruption of cortical-striatal circuitry. Mechanisms of cell death are unclear, but processes involving mitochondrial abnormalities, excitotoxicity, and abnormal protein degradation have been implicated. Many factors likely contribute to neuron death and dysfunction, and this has made it difficult to systematically address the pathology in HD. Pharmaceutical therapies are commonly used in patients to treat disease symptoms. These have limited benefit and do not address the inexorable disease progression. Several neuroprotective therapies are being evaluated in animal models of HD as well as in clinical trials. Similarly, cell replacement strategies such as fetal transplantation have been used in the clinic with minimal success, making future cell replacement strategies such as stem cell therapy uncertain. This review describes the disease pathology in HD and addresses many of the past and emerging therapeutic strategies.     

自身免疫性胰腺炎

The purpose of this review is to provide a concise view of the existing knowledge of autoimmune pancreatitis (AIP) for practicing clinicians.AIP is a rare disease whose recognition and understanding are evolving.It is a type of chronic pancreatitis which often presents as obstructive jaundice,has a distinctive histology and is exquisitely sensitive to steroid therapy.This form of chronic pancreatitis has a unique clinical,biochemical,and radiological profile.The term “AIP” encompasses two subtypes:type 1 and type 2.Type 1 AIP is the pancreatic manifestation of a systemic fibro-inflammatory disease called IgG4 associated systemic diseases; type 2 AIP has been shown to be associated with inflammatory bowel disease.Existing criteria are geared towards the diagnosis of type 1 AIP.At present,pancreatic histology is a requirement for the definitive diagnosis of type 2 AIP.AIP can mimic most other pancreatic diseases in its presentation,but in clinical practice it often has to be differentiated from pancreatic cancer.There are established criteria and algorithms not only to diagnose AIP but also differentiate it from pancreatic cancer.The utility of these algorithms and the approach to management are discussed here.     

Corticobasal degeneration

Opinion statement  Corticobasal degeneration (CBD) is a neurodegenerative disorder characterized clinically by a combination of cortical and basal ganglia signs. Pathologically, it is classified as a tauopathy. The most distinctive clinical feature is its unilateral or markedly asymmetric presentation; among parkinsonian syndromes, with rare exceptions, only Parkinson’s disease presents with such asymmetry. The most common presenting cortical features include apraxia (patients often complain of a “useless” limb), aphasia (usually nonfluent), parietal lobe sensory signs (agraphesthesia, extinction, astereognosis), frontal dementia, or myoclonus. Basal ganglia signs include rigidity, akinesia, limb dystonia, and postural instability. The diagnosis is often challenging for three reasons: 1) The full complement of findings are rarely seen at presentation; 2) If CBD is not suspected, subtle but relevant findings (eg, extinction, language impairment, myoclonus, or apraxia) may not be searched for or appreciated; 3) The clinical picture of CBD has substantial overlap with a variety of other parkinsonian and dementing illnesses. The differential diagnosis includes Parkinson’s disease, progressive supranuclear palsy, frontotemporal dementia, primary progressive aphasia, and Alzheimer’s disease. The clinical diagnosis is not confirmed pathologically in up to half of cases, so the term corticobasal syndrome is often preferred during life, reserving the term corticobasal degeneration for pathologically verified cases. Treatment of CBD is primarily supportive, and most patients die within 10 years of onset. Parkinsonian signs may improve to a modest degree with levodopa, clonaze pam can suppress myoclonus, and botulinum toxin can relieve dystonia. Early speech therapy, physical therapy, and occupational therapy, as well as assist devices such as a rolling walker may improve functioning and reduce complications such as aspiration pneumonia and falls. With time, however, most patients lose their independence and mobility. Throughout the course of the illness (particularly when it is advanced), caring for the caregiver is as important as caring for the patient.     

Erythromelalgia

Erythromelalgia is an extraordinary disorder of unknown etiology and pathophysiology that resembles the post-traumatic reflex dystrophy syndromes but has not been described previously in the orthopedic literature. Its distinctive triad of intense burning extremity pain associated with erythema and increased skin temperature are diagnostic. Primary or idiopathic and a secondary or associated form have been identified. The latter occurs in association with an underlying disease process, especially myeloproliferative disorders. Treatment with pharmacologic agents and surgery are ineffective except in the secondary group where treatment of the associated disorder generally results in a remission. Symptoms in the primary group can be minimized by appropriate environmental control with cooling and avoiding heat-producing situations that would raise skin temperature above a critical thermal threshold.     

Liver transplantation in patients with Caroli's disease and recurrent cholangitis

Caroli's disease is an uncommon congenital disorder of the intrahepatic biliary tree. It is characterized by multiple and segmental dilatations of the bile ducts. The clinical course of Caroli's disease is often complicated by recurrent episodes of bacterial cholangitis that seriously impair the patient's quality of life. Despite wide spectrum antimicrobial agents, medical treatment of cholangitis is frequently unsuccessful in patients with Caroli's disease due to the persistence of bacteria in dilatated bile ducts. Other therapies, including internal or external biliary drainages and various surgical or endoscopic procedures, have been used in the treatment of Caroli's disease, with poor results. There are no previous reports in the literature of liver transplantation for recurrent cholangitis in patients with Caroli's disease. We present two such cases, in which cholangitis is resolved. Received: 16 July 1996 Received after revision: 4 February 1997 Accepted: 5 February 1997     

Lyme disease.

Lyme disease, a multisystem disorder, has now been reported to the Centers for Disease Control from 43 states of the United States. The disease is a tick-transmitted infectious disorder caused by the spirochete bacterium Borrelia burgdorferi. Lyme disease typically begins with the symptoms of flu associated with a characteristic skin rash, erythema chronicum migrans. The diagnosis of Lyme disease is best made by clinical examination and epidemiologic history, with serologic studies supporting the clinical diagnosis. Prompt diagnosis and early treatment with antibiotics will often lead to the resolution of symptoms and the prevention of late complications, Lyme carditis, neurologic manifestations, and arthritis.     

Renal pathology in children with mitochondrial diseases

We studied renal involvement in 42 children with mitochondrial diseases (MDs). The diagnosis of MD was established by morphological, biochemical, and molecular genetic criteria. Renal disease was considered when patients had renal failure, nephrotic syndrome, Fanconis syndrome or any symptomatic renal alteration. Mild tubular disorder was established if they had abnormal laboratory findings with no apparent clinical symptom. Renal involvement was found in 21 children (50%), of whom 8 had an apparent clinical picture and 13 a mild tubular disorder. Five patients with renal disease showed Debré–Toni–Fanconis syndrome, 2 of them with decreased glomerular filtration rate (GFR). One case had nephrotic syndrome, another one presented decreased GFR, and the last one had a neurogenic bladder and bilateral hydronephrosis. Patients with mild renal disease showed tubular dysfunction with normal GFR. Renal involvement is frequent and present in about half of the children with MD. Thus, studies for evaluating kidney function should be performed on children with MD. Conversely, patients with tubulopathy of unknown origin or progressive renal disease should be investigated for the existence of MD, especially if associated with involvement of other organs or tissues. Southern blot analysis to search for large-scale mitochondrial DNA (mtDNA) rearrangements should be performed for patients with MD and kidney involvement.     

Membranous nephropathy in Schimke immuno-osseous dysplasia

Schimke immuno-osseous dysplasia is a rare autosomal recessive multi-system disorder, with clinical features of growth retardation, spondylo-epiphyseal dysplasia, nephrotic syndrome and immunodeficiency beginning in childhood. Here, we report a new case, in a 10-year-old boy with characteristic symptoms of Schimke immuno-osseous dysplasia. The patient presented with short stature and, later, developed nephrotic syndrome and peritonitis. In addition, he had perinuclear anti-neutrophilic cytoplasmic antibody (p-ANCA)-positive arthritis. Renal pathology of the patients with this disease usually show focal segmental glomerulonephritis, whereas our patient had membranous nephropathy, which has not previously been reported.     

CD10: a valuable tool for the light microscopic diagnosis of microvillous inclusion disease (familial microvillous atrophy)

Microvillous inclusion disease (MID) is a specific disorder of the intestinal brush border that leads to intractable secretory diarrhea in infants. At present, electron microscopic analysis is required for its definitive diagnosis. However, this technique is not always available or feasible, and the diagnostic microvillous inclusions may not be evident in all specimens. Accordingly, the availability of a panel of histochemical and immunohistochemical stains displaying a specific staining pattern for MID will allow pathologists to reach a definitive diagnosis of this disorder without recourse to electron microscopy. CD10 is a membrane-associated neutral peptidase, shown to have a linear brush-border staining pattern in normal small intestine. We studied the staining pattern of CD10 in small intestinal biopsies from six patients with MID and in 24 control cases (10 normal small intestine, 10 celiac disease, two autoimmune enteropathy, and two allergic enteropathy). All MID cases revealed prominent cytoplasmic CD10 immunoreactivity in surface enterocytes. In contrast, all control cases showed linear brush-border staining. Similar results were obtained with periodic acid-Schiff, polyclonal carcinoembryonic antigen, and alkaline phosphatase, three stains known to show cytoplasmic staining of surface enterocytes in MID. In conclusion, CD10 is a valuable tool for the diagnosis of MID. It may be used as part of a panel that includes other stains with a distinctive staining pattern in MID such as periodic acid-Schiff, polyclonal carcinoembryonic antigen, and alkaline phosphatase. We suggest that the definitive diagnosis of MID can be reached when small bowel biopsies from infants with intractable diarrhea display cytoplasmic staining of surface enterocytes with the above-mentioned stains.     

Lactic acidosis in the setting of antiretroviral therapy for the acquired immunodeficiency syndrome. A case report and review of the literature

Type B lactic acidosis, a rare but often fatal disorder, has been reported in 21 AIDS patients on antiretroviral therapy (ART). We present an AIDS patient with severe and prolonged lactic acidosis on stavudine and lamivudine. The lactic acidosis occurred in the absence of mitochondrial myopathy, hepatomegaly, or liver failure. This is the second report of lactic acidosis in a patient on stavudine and lamivudine. This patient recovered after aggressive supportive therapy including intravenous alkali and fluid administration as well as continuous venovenous hemodiafiltration. A single dose of dichloroacetate (DCA) was associated with a decrease in the serum lactate level by 20%, which persisted for more than 24 h. Seventeen months after recovery, the patient was rechallenged with ART without recurrence of lactic acidosis. We review and summarize all reported cases of patients with ART-associated lactic acidosis reported in the English literature.     

Antineutrophil cytoplasmic autoantibodies and associated diseases: a review

Antineutrophil cytoplasmic autoantibodies (ANCA) are specific for constituents of neutrophil primary granules and monocyte lysosomes. There are different types of ANCA with different specificities. By indirect immunofluorescence microscopy using alcohol-fixed neutrophils as substrate, two major categories of ANCA can be recognized, one with cytoplasmic staining (C-ANCA) and the other with artifactual perinuclear staining (P-ANCA). Some C-ANCA have specificity for proteinase 3 (PR3-ANCA) and some P-ANCA have specificity for myeloperoxidase (MPO-ANCA), but there are additional C-ANCA and P-ANCA specificities. ANCA are found in the blood of patients with necrotizing systemic vasculitis, such as Wegener's granulomatosis and polyarteritis nodosa, and patients with idiopathic crescentic glomerulonephritis. The glomerular lesion in patients with systemic and renal-limited ANCA-associated diseases is the same, ie, a pauci-immune necrotizing and crescentic glomerulonephritis. No matter where the vascular lesions of ANCA-associated disease are (eg, kidney, lung, gut, muscle, skin), they are characterized by necrotizing inflammation and a paucity of immune deposits. The distribution of disease correlates to a degree with the ANCA specificity, although there is substantial overlap. For example, patients with Wegener's granulomatosis most often have C-ANCA and patients with renal-limited disease most often have P-ANCA. In patients with P-ANCA-associated glomerulonephritis, approximately 90% of the P-ANCA have specificity for MPO. The clinical manifestations of ANCA-associated diseases often begin following a flu-like illness. The onset is most often in the winter and least often in the summer. The renal disease usually presents as rapidly progressive renal failure with nephritis. One of the most life-threatening components of the systemic involvement is pulmonary hemorrhage caused by a necrotizing alveolar capillaritis. Intravenous cyclophosphamide plus steroids is as effective as oral cyclophosphamide plus steroids for controlling ANCA-associated diseases. Using life-table analysis, the 2-year patient and renal survival rate in both patients with renal-limited and systemic disease is greater than 70%. There is evidence that in addition to being a useful serologic marker, ANCA are directly involved in the pathogenesis of the vascular injury in patients with ANCA-associated diseases. Although ANCA antigens are normally in the cytoplasm of neutrophils and monocytes, priming of these cells, as occurs following exposure to certain cytokines, results in the release of small amounts of ANCA antigens at the cell surface. In vitro, ANCA-IgG causes cytokine-primed neutrophils to undergo a respiratory burst and degranulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Progressive tubulointerstitial nephritis and chronic cholestatic liver disease

We report the clinical and morphological features of a distinctive hepatorenal disorder in four patients and review the five similar patients in the literature. The main clinical characteristics were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis leading to renal death in early childhood. Liver histology showed disturbed architecture with nodular and acinar formations and portal fibrosis and bile duct proliferation. Histological abnormalities in the kidney were severe interstitial fibrosis and tubular atrophy and dilatation, while the typical features of nephronophthisis were lacking. These clinical and morphological characteristics distinguish our patients from the majority described, as having nephronophthisis and congenital hepatic fibrosis or any other known syndrome with concomitant hepatorenel involvement. We suggest that the association of cholestatic liver disease and progressive tubulointerstitial nephritis represents a new syndrome.     

Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant

Pathologic diagnosis of pancreatic adenocarcinoma is frequently a challenge, particularly in small biopsies, frozen sections, and in metastatic foci. Here we report a deceptively benign-appearing and morphologically distinctive pattern of ductal adenocarcinoma with prominent microvesicular cytoplasm, giving the cells a foamy appearance similar to that described in the prostate (Am J Surg Pathol 1996;20:419). This variant, which we refer to as foamy gland pattern (FGP), was frequently misdiagnosed in frozen sections or biopsies and its pathologic stage underestimated in surgical specimens. Histologically, the diagnostic features were: (1) white and crisply foamy, "microvesicular" cytoplasm; (2) often basally located and compressed, hyperchromatic nuclei reminiscent of endocervical glands (and so-called "adenoma malignum") or gastric foveolar glands; (3) irregular nuclear contours forming wrinkled (raisinoid) nuclei in some areas; and (4) a distinctive chromophilic condensation of the cytoplasmic material in the luminal aspect of the cells forming a brush border-like zone (BLZ). Histochemically, this BLZ was positive for mucicarmine, alcian blue, and high iron diamine, but not PAS. The remainder of the cytoplasm was negative for all these stains. In contrast, benign mucinous ducts, which constitute the major differential diagnosis, had more homogeneous acidophilic cytoplasm, lacked BLZ, and showed cytoplasmic staining with PAS. Immunohistochemically, the tumor cells were diffusely and strongly positive for CEA and cytokeratin 8 whereas B72.3 staining was focal and weak. MUC1 staining was largely confined to the BLZ. MUC2 was negative. P53 staining was detected in 16 of the 20 cases studied and was strong and diffuse in five. K-ras mutation was detected in 6 of 8 cases studied. The clinical findings in the 20 patients in this study (4 pure and 16 mixed with usual ductal carcinoma) did not appear to differ significantly from those of ordinary ductal adenocarcinoma of the pancreas. Eleven patients were men and nine were women; the mean age was 62 years and the mean tumor size was 4.4 cm. Follow-up information was available in 17 patients of whom 7 were alive at an average follow up of 23 months (range, 7-104 mos), and 10 were dead of disease at a median follow up of 15 months (range, 4-42 mos). The median survival of the four patients with pure FGP was 18 months. The median survival did not appear to be significantly longer than that of the patients with resectable ordinary ductal adenocarcinoma in the authors' experience (109 patients, median survival of 12 mos, p = 0.48). In conclusion, foamy gland pattern of invasive pancreatic ductal carcinoma is morphologically distinctive and is prone to misdiagnosis as a benign process. The pathologic stage is often underestimated as a result of the lack of its recognition and misinterpretation as mucinous ducts. Careful attention to its microscopic features is adequate for accurate diagnosis. Histochemical and immunohistochemical stains are useful in confirming the diagnosis of malignancy in challenging cases.     

Chediak-higashi syndrome presenting in accelerated phase

Chediak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder, characterized by silver hair, recurrent infections, partial oculo-cutaneous albinism, mild coagulation defect and progressive neuropathy. The characteristic feature of CHS is the presence of huge lysosomes and cytoplasmic inclusions within different body cells like the white blood cells. The disease has an early onset but usually presents in an accelerated phase. We present a case of a 2 years old boy with high grade fever, bilateral cervical lymphadenopathy, hepatosplenomegaly, abdominal distention of 28 days duration. He was diagnosed with Chediak-Higashi syndrome in accelerated phase on the basis of clinical presentation, morphological findings on peripheral blood film and bone marrow aspirate.     

Body Dysmorphic Disorder: Suggestions for Detection and Treatment in a Surgical Dermatology Practice

BACKGROUND: Body dysmorphic disorder is a relatively common condition in patients seeking elective surgery. Little has been written, however, in the dermatologic surgery literature about body dysmorphic disorder, where proper recognition and management of this disorder is needed during this time of increased demand for aesthetic dermatologic surgery. OBJECTIVE: The objective was to review the prevalence, demographics, clinical features, treatment approaches, and referral suggestions for patients with body dysmorphic disorder in an attempt to facilitate care of such patients in a general dermatologic surgical practice. METHODS: We reviewed the dermatologic, cosmetic surgical, and psychiatric literature regarding body dysmorphic disorder and related disorders. RESULTS: Body dysmorphic disorder is observed in 6% to 15% of dermatologic and cosmetic surgery patients and in 2% of the general population. Surgical treatment of patients with body dysmorphic disorder typically leads to no change or worsening of symptoms in the majority of patients. The use of screening questionnaires and observation for hallmark features are helpful for clinicians in managing patients with body dysmorphic disorder. Psychiatric referral is desirable, because cognitive behavioral therapy and pharmacologic intervention with selective serotonin reuptake inhibitors are often efficacious. CONCLUSIONS: Body dysmorphic disorder is often underdiagnosed and suboptimal management is common. Effective treatment consists of behavioral and pharmacologic intervention. Use of the Dufresne Body Dysmorphic Disorder Questionnaire appears to be useful as a screening tool in an outpatient setting, and awareness of clinical features of body dysmorphic disorder in the dermatologic surgical setting may spare patients significant morbidity while allowing surgical dermatologists to manage their patients and practices more effectively.     

Diagnostic classification of antineutrophil cytoplasmic autoantibody-associated vasculitides

Antineutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of patients with a variety of clinically and pathologically distinctive forms of necrotizing vasculitis. Some patients have classic manifestations of well-recognized clinicopathologic syndromes, such as Wegener's granulomatosis, microscopic polyarteritis nodosa, and Churg-Strauss syndrome, but many patients are difficult to assign to a diagnostic category. The Ad Hoc Nomenclature Committee of The Third International Workshop on ANCA is attempting to identify a working classification system for ANCA-associated vasculitides. This system takes into account the many shared clinical and pathologic features, and relies on prerequisite positive and negative findings for diagnostic categorization.     

Infrahepatic hematoma secondary to gangrenous cholelithiasic hemocholecyst treated with antivitamins K

Acute haemocholecyst is a rare disorder but often reported in patients with gallstones. Rupture of the gallbladder causing hypovolaemic shock secondary to massive intraperitoneal bleeding has been reported in about fifty patients to date. We report a new case of haemocholecyst with rupture of the gallbladder in a patient with gallstones treated by anticoagulant therapy. This case is unusual in terms of the nature of the gallbladder disease: massive gangrene with complicating hemorrhage and destruction of deficient regions of the wall of the gallbladder induced an infrahepatic haematoma without hypovolemic shock, in contrast with the massive intraperitoneal hemorrhage reported in other cases.     

Mitochondrial disease—an important cause of end-stage renal failure

Kidneys are highly aerobic organs. They receive roughly a quarter of the cardiac output and contain a high density of mitochondria, particularly in the cortical tubules, which are required to produce adenosine triphosphate (ATP) in sufficient quantity to power the re-uptake of over 98 % of the filtered load. Given the dependence of renal function on aerobic metabolism, it is not surprising that impairment of normal mitochondrial function—due to insults such as ischaemia, drug toxicity and genetic mitochondrial disease—can lead to kidney failure. In this edition of Pediatric Nephrology, D’Aco and colleagues (doi:10.1007/s00467-012-2354-y) describe a patient who developed end-stage renal failure caused by a pathogenic mutation (m.586G?>?A) in the gene encoding the mitochondrial tRNA for phenylalanine, which adversely affects the translation of mitochondrial DNA. The pathogenicity of this mutation was confirmed in cybrid studies using fibroblasts obtained from the patient. In light of this report, m.586G?>?A should now be added to the rapidly expanding list of mitochondrial and nuclear gene mutations causing mitochondrial disease with renal involvement. Furthermore, mitochondrial disease should be considered as an underlying aetiology in cases of unexplained renal failure, particularly in the context of a multisystem disorder. Renal replacement therapy is an option for patients with mitochondrial disease, but life expectancy even with this therapy may be limited by co-morbidities.