Prospective trial of operative versus non-operative treatment of severe vesicoureteric reflux in children: five years' observation. Birmingham Reflux Study Group.

Children with severe vesicoureteric reflux were allocated randomly to either operative or non-operative treatment and followed up. Altogether 161 children were observed for two years, of whom 104 were followed up for five years. Reflux was abolished in 98% of ureters reimplanted, but more than half of the patients treated non-operatively continued to show severe reflux at five years. Two patients progressed to end stage renal failure, and a further four with extensive bilateral renal scarring became hypertensive. There were no significant differences between treatment groups in the incidence of breakthrough urinary infection, renal excretory function and concentrating ability, renal growth, progression of existing renal scars, or new scar formation. Progressive scarring occurred at all ages but was significantly more common during the first two years'' observation. Furthermore, new scars developed exclusively during the first two years'' observation, affecting 10 children aged 2-7 at allocation. Neither treatment can claim superiority or fully protect the kidneys from further damage, and efforts must continue to be directed towards identifying those at risk before scarring develops.     

NONOBSTRUCTIVE OLIGURIA—Differential Diagnosis

A review is presented of ten years'' experience with the differential diagnosis of oliguria, utilizing the standard tests of renal function with the addition of the phenolsulfonphthalein excretion and urinary chloride measurements. The histories of 60 patients seen in consultation because of 24-hour urinary volume of less than 400 ml were studied in order to clarify the value of these tests. Particular attention was given to the postoperative “dilution state,” the oliguria of which tends to mimic that of “acute tubular necrosis.”In only 25 per cent of the 60 cases was “acute tubular necrosis” responsible for the oliguria. In the remaining 75 per cent of patients, oliguria was due either to the effects of simple dehydration without tubular damage, or to tubular dysfunction on a physiologic rather than an organic basis. Thus, three out of four patients with oliguria required aggressive and specific fluid-electrolyte therapy, often with the intensive use of potassium. One out of four required the opposite in therapy—controlled dehydration without added potassium and, on occasion, peritoneal or extracorporeal dialysis, in order to allow six to ten days for tubular repair.     

La stérilité d'origine immunologique.

Antispermatozoal antibodies in the woman, the man, or both, may be the cause of nonorganic infertility in a small number of couples. The antibodies are most often found in the serum or in the genital fluids. Diagnosis is based on the postcoital test and on various laboratory tests to assess sperm-cervical mucous compatibility and to detect antispermatozoal antibodies. In women the strongest relation between results of laboratory tests and infertility is between the presence of serum antispermatozoal antibodies and infertility of more than 3 years'' duration. In men there is a relation between high levels of these antibodies in the semen and infertility. Various treatments have been proposed, but further prospective studies are needed. However, promising results have been reported with homologous intrauterine insemination and with immunosuppression in men.     

Viral Antibodies in Diabetes Mellitus

Sera from 123 patients with diabetes mellitus of recent onset, 155 patients with diabetes of more than two years'' duration, and 250 normal persons were collected over a period of two and a half years. All sera were tested for neutralizing antibody to Coxsackie virus types B1–6, and a sample was tested for complement-fixing antibody to a number of viral, rickettsial, and mycoplasmal antigens.In diabetics of recent onset no evidence was found of any excess of antibodies to mumps virus or some common respiratory viruses. Insulin-dependent diabetes within three months of onset were found to have higher antibody titres to Coxsackie B virus, particularly of type B4, than either normal subjects or patients with diabetes of longer duration.     

ECTOPIC PREGNANCY—Early Diagnosis,Clinical Errors and Conservative Operation

This report of eight years'' experience with extrauterine pregnancy by a single gynecologist is an exposition of how the diagnosis was made or why it was missed.Of 26 diagnoses of ectopic pregnancy, five were false (20 per cent); and in three cases (10 per cent) the diagnosis was not made promptly—a total error of 30 per cent.Ectopic pregnancy will be discovered earlier if obstetric patients are always examined shortly after missing the first menstrual period.A palpable adnexal mass was present in 19 of 21 ectopic pregnancies (90 per cent). A mass was palpable in only one of five cases erroneously diagnosed as ectopic pregnancy (20 per cent).Decidual casts were passed by four patients, two of whom did not have ectopic pregnancy.If two gynecologists do not agree on the question of extrauterine pregnancy, a third opinion should be sought or culdoscopy employed.Enucleation of the conceptus and salvage of the oviduct is advocated.     

Beneficial effects of angiotensin converting enzyme inhibition on renal function in patients with diabetic nephropathy.

The effects of angiotensin converting enzyme inhibition with captopril were investigated in patients with diabetic nephropathy and hypertension. After nine days'' treatment with captopril glomerular filtration rate was unchanged in 13 patients, whereas renal plasma flow had increased from 265 to 302 ml/min/1.73 m2 body surface area (p less than 0.05) and the filtration fraction had decreased from 14.3 to 12.8% (p less than 0.025). During two years'' treatment with captopril in 14 patients the mean arterial blood pressure had fallen by 5 mm Hg (p less than 0.005) and the deterioration in glomerular filtration rate had decreased from 10.3 to 2.4 ml/min/year (p less than 0.005). There was no correlation between the fall in blood pressure and the reduction in the deterioration of glomerular filtration rate. These findings suggest that the effects of angiotensin converting enzyme inhibition on renal haemodynamics protect renal function. Inhibitors of angiotensin converting enzyme should be considered for lowering blood pressure in patients with diabetic nephropathy.     

Acute leukaemia after busulphan.

During a double-blind study of two years'' cytotoxic chemotherapy with busulphan or cyclophosphamide in patients who had had resection of carcinoma of the bronchus the long-term effects of these two drugs were also studied. Four of the 243 patients treated with busulphan developed leukaemia compared with none of the 234 treated with cyclophosphamide and none of the 249 on placebo. None of these four patients received radiotherapy or other cytotoxic chemotherapy before leukaemia was diagnosed, and all four were among the 19 patients who developed pancytopenia while taking busulphan, five to eight years before leukaemia became clinically apparent. These findings suggest that busulphan is leukaemogenic, though its mode of action is uncertain.     

Sarcoidosis in coexistence with Toxoplasma gondii invasion]

Two cases of sarcoidosis with peripheral lymphatic nodes involvement and coexisting toxoplasmosis are presented. Both cases illustrate diagnostic and differentiating problems in patients with chronic lymphatic nodes enlargement and positive serological reaction to T. gondii antigen. An emphasis is on the importance of the histological examination of the lymphatic nodes for the sarcoidosis diagnosis and contribution of T. gondii to the disease. Positive serological reaction to T. gondii antigen in patients with sarcoidosis may reflect inactive toxoplasmosis; however, periodical serological tests are necessary monitoring the due immunosuppressive treatment used in patients with sarcoidosis.     

Scleroderma and Primary Biliary Cirrhosis

Two cases of scleroderma and primary biliary cirrhosis are described. One had systemic sclerosis with primary biliary cirrhosis of six years'' duration at the stage of ductular proliferation. The other had the C.R.S.T. syndrome (calcinosis, Raynaud''s phenomenon, sclerodactyly, and telangiectases) with primary biliary cirrhosis at the florid stage. Several similar cases were found in a review of other reports, and it is suggested that the association may be due to a common “autoimmune” process.     

Linkage of type I interferon activity and TNF-alpha levels in serum with sarcoidosis manifestations and ancestry

Background

Both type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes.

Methods

We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman''s rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations.

Results

Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups.

Conclusions

Our data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease.     

The lupus syndrome induced by hydralazine: a common complication with low dose treatment.

The true incidence of the lupus syndrome induced by hydralazine was determined in a longitudinal study of 281 patients consecutively starting hydralazine for hypertension over a 51 month period. Data on the duration of treatment and the maximum dose achieved were examined using life table analysis. After three years'' treatment with hydralazine the incidence of the lupus syndrome was 6.7% (95% confidence limits 3.2-10.2%). The incidence was dose dependent, with no cases recorded in patients taking 50 mg daily and incidences of 5.4% with 100 mg daily and of 10.4% with 200 mg daily. The incidence was higher in women (11.6%) than in men (2.8%). In women taking 200 mg daily the three year incidence was 19.4%. Hydralazine is an effective antihypertensive drug that has come to be used in restricted dosage (not more than 200 mg daily) because of its risk of inducing the lupus syndrome. This study shows that the true incidence of the syndrome is still unacceptably high even when the drug is prescribed according to current recommendations.     

Perceptual expertise in forensic facial image comparison

Forensic facial identification examiners are required to match the identity of faces in images that vary substantially, owing to changes in viewing conditions and in a person''s appearance. These identifications affect the course and outcome of criminal investigations and convictions. Despite calls for research on sources of human error in forensic examination, existing scientific knowledge of face matching accuracy is based, almost exclusively, on people without formal training. Here, we administered three challenging face matching tests to a group of forensic examiners with many years'' experience of comparing face images for law enforcement and government agencies. Examiners outperformed untrained participants and computer algorithms, thereby providing the first evidence that these examiners are experts at this task. Notably, computationally fusing responses of multiple experts produced near-perfect performance. Results also revealed qualitative differences between expert and non-expert performance. First, examiners'' superiority was greatest at longer exposure durations, suggestive of more entailed comparison in forensic examiners. Second, experts were less impaired by image inversion than non-expert students, contrasting with face memory studies that show larger face inversion effects in high performers. We conclude that expertise in matching identity across unfamiliar face images is supported by processes that differ qualitatively from those supporting memory for individual faces.     

Mycobacterium tuberculosis DNA in tissue affected by sarcoidosis.

OBJECTIVE--To investigate the prevalence of Mycobacterium tuberculosis DNA in granulomatous tissues from patients with sarcoidosis and from controls matched for age, sex, and tissue by using the polymerase chain reaction. DESIGN--Single blind control trial. SUBJECTS--16 patients with sarcoidosis who had undergone diagnostic biopsy of lung, skin, or lymph node and 16 patients with squamous cell carcinoma or Hodgkin''s disease to act as controls. In addition, four lung specimens infected with M tuberculosis were included as positive controls. RESULTS--M tuberculosis DNA was present in sarcoid tissues containing granulomas from seven of the 16 patients and one of the 16 matched controls. Two of the four specimens known to be infected with M tuberculosis were positive in the controlled experiment. CONCLUSION--These figures suggest that M tuberculosis DNA is detected as readily in patients with sarcoidosis as in patients with frankly tuberculous tissues and imply that M tuberculosis may be linked to the cause of sarcoidosis.     

Defective blood glucose counter-regulation in diabetics is a selective form of autonomic neuropathy.

Administration of a low-dose insulin infusion to normal subjects results in a mild drop in blood glucose concentration (1.1 mmol/1 (20 mg/100 ml)) and the resetting of the basal glucose at the lower concentration. Clinical hypoglycaemia does not develop, and there is a significant release of glucagon, growth hormone, and cortisol. A similar infusion in insulin-requiring diabetics results in hypoglycaemia accompanied by a release of growth hormone and cortisol but no significant release of glucagon. Subsequently giving arginine to these patients results in a significant release of glucagon, indicating that the alpha cell is intact and can respond to local, direct stimulation. In one patient the defect in glucagon response to impending hypoglycaemia developed after two years'' insulin treatment. This type of dissociated response'' of the alpha cell has been reported in animals after denervation of the pancreas, and insulin-requiring diabetics may develop a selective form of autonomic neuropathy affecting the vagal control of glucagon release.     

Immunoresponsiveness in Ulcerative Colitis and Crohn's Disease—Effect of Colectomy and Suppression of Disease Activity

We evaluated the effect of medically induced symptomatic disease improvement on in vitro tests of cell-mediated immune responses in 33 patients with Crohn''s disease. When results obtained in 17 patients with ulcerative colitis were compared with those of 10 patients with ulcerative colitis who had undergone a colectomy, no significant correlation was detected between individual clinical and laboratory variables or the Crohn''s disease activity index and in vitro tests of cell-mediated immunity. A different pattern emerged from the longitudinal tests of cell-mediated immunity: when these test results were initially abnormal in patients with Crohn''s disease, clinical improvement as assessed by the Crohn''s disease activity index was associated with normalizing cell-mediated immunity. In contrast, when the test results were initially normal, clinical improvement was not associated with any change in the immune response. Following colectomy in patients with ulcerative colitis, some abnormalities of suppressed immune responses remained, although patients were cured of their disease. Factors other than clinical disease activity may be responsible for the suppressed immunoresponsiveness in some patients with inflammatory bowel disease, and variable changes in cell-mediated immunity occur after both surgical and medical treatment.     

Screening for Inherited Metabolic Disease by Plasma Chromatography (Scriver) in a Large City

Before introducing a more comprehensive screen such as plasma chromatography, with its potential to detect 20 amino-acid disorders—an advantage over screening methods which detect only phenylketonuria—the greatly increased problems of organization and the effect on the community, midwives, paediatric services, and laboratory should be considered. The three years'' experience in Birmingham showed a three-fold increase in cases detected and suggests criteria for further investigation and treatment.     

In-vitro Inhibition of Leucocyte Migration in Crohn's Disease by a Sarcoid Spleen Suspension

A Kveim suspension has been shown to inhibit the migration of leucocytes in vitro from 12 out of 18 patients with Crohn''s disease but to have no comparable effect on leucocytes from patients with ulcerative colitis or from a group of patients with other diseases. These findings provide further evidence of cross-reactivity or of a possible aetiological link between Crohn''s disease and sarcoidosis and suggest a further immunological distinction between Crohn''s disease and ulcerative colitis.     

No evidence of altered alveolar macrophage polarization,but reduced expression of TLR2, in bronchoalveolar lavage cells in sarcoidosis

Background

Sarcoidosis is a granulomatous inflammatory disease, possibly of infectious aetiology. We aimed to investigate whether the degree of functional polarization of alveolar macrophages (AMs), or Toll-like receptor (TLR) expression, is associated with sarcoidosis or with distinct clinical manifestations of this disease.

Methods

Total BAL cells (cultured four or 24 h in medium, or stimulated 24 h with LPS) from 14 patients and six healthy subjects, sorted AMs from 22 patients (Löfgren''s syndrome n = 11) and 11 healthy subjects, and sorted CD4+ T cells from 26 patients (Löfgren''s syndrome n = 13) and seven healthy subjects, were included. Using real-time PCR, the relative gene expression of IL-10, IL-12p35, IL-12p40, IL-23p19, CCR2, CCR7, iNOS, CXCL10, CXCL11, CXCL16, CCL18, CCL20, CD80, and CD86, and innate immune receptors TLR2, TLR4, and TLR9, was quantified in sorted AMs, and for selected genes in total BAL cells, while IL-17A was quantified in T cells.

Results

We did not find evidence of a difference with regard to alveolar macrophage M1/M2 polarization between sarcoidosis patients and healthy controls. TLR2 gene expression was significantly lower in sorted AMs from patients, particular in Löfgren''s patients. CCL18 gene expression in AMs was significantly higher in patients compared to controls. Additionally, the IL-17A expression was lower in Löfgren''s patients'' CD4+ T cells.

Conclusions

Overall, there was no evidence for alveolar macrophage polarization in sarcoidosis. However, there was a reduced TLR2 mRNA expression in patients with Löfgren''s syndrome, which may be of relevance for macrophage interactions with a postulated sarcoidosis pathogen, and for the characteristics of the ensuing T cell response.     

糖尿病足患者睡眠质量与疲劳程度的调查研究

目的:调查糖尿病足(diabetic foot,DF)患者的睡眠质量与疲劳程度,并分析其相关性。方法:选取105例糖尿病足患者,采用人口数据统计表调查患者的一般情况,匹兹堡睡眠质量指数量(PSQI)评估患者的睡眠质量,Piper疲劳量表(PFS)评估患者的疲劳程度,并通过pearson检测分析其相关性。结果:人口统计数据显示,56%的DF患者年龄在41岁以上,64.8%女性,82.9%已婚,48.6%小学学历,39%病程3年或更长的时间。PSQI的平均总得分为(8.17±3.02),PFS量表总分为(6.38±2.18),睡眠质量与疲劳度总得分之间呈显著正相关,相关系数r=0.622(P0.05)。结论:DF患者的睡眠质量较差,大多出现中度疲劳,二者之间呈正相关,应加强对DF患者的睡眠质量与疲劳的护理。