Lung carcinoid related Cushing's syndrome: report of three cases and review of the literature

Three patients with lung carcinoid related Cushing''s syndrome (LCRCS) treated at Frenchay Hospital, Bristol between 1984 and 1994 are described. The first patient presented with hyperpigmentation 13 years after bilateral adrenalectomy. The second patient had no recurrence or metastases 14 years after removal of a typical carcinoid tumour. The last patient survived nine years after diagnosis of liver metastasis. The possibility of LCRCS should be considered in every patient proved to have Cushing''s disease and bilateral adrenal enlargement on abdominal computed tomography. Biochemical sets of investigation (for example, adrenocorticotrophic hormone (ACTH) stimulation, dexamethasone suppression, and metyrapone response) could be misleading and should not be relied upon solely. Search for an ectopic ACTH source should be called off only when ACTH has been demonstrated in the surgically removed specimen, and most importantly, when the serum ACTH concentration returns to normal after surgery. Lung carcinoid tumours are compatible with long survival, and liver metastasis could prove indolent and slowly growing.


     

Primary antibody deficiency and Crohn's disease

Five patients with primary antibody deficiency were investigated because of intermittent but persistent diarrhoea of several years duration despite immunoglobulin replacement therapy. We found no evidence of Giardia lambia or other intestinal pathogens to explain their gastrointestinal symptoms. All five had definite radiological evidence of small bowel Crohn''s disease and three had histological specimens available with abnormalities consistent with Crohn''s disease. One patient had a non-caseating granuloma in an oral ulcer. A second patient with stricturing disease in the small bowel had a mucosal inflammatory infiltrate with non-caseating granulomas. A third had transmural inflammation but no granulomas. All five patents were diagnosed as having Crohn''s disease and have responded symptomatically to steroid therapy.


     

Management of non-Hodgkin's lymphomas

The non-Hodgkin''s lymphomas (NHL) are a heterogenous group of disorders characterised by malignant proliferation of lymphoid cells. The cellular origin is relatively well established with subtypes corresponding to the various stages of lymphocyte differentiation. The term encompasses a hotchpotch of conditions with very different morphological appearance, behaviour and clinical outcome. NHL comprise 2.4% of all cancers, with incidence increasing with age. The commonest presentation is with progressive lymphadenopathy, though extranodal manifestations are present in a significant proportion. The clinical behaviour ranges from a benign, indolent course to rapidly progressive disease; prognosis varies from weeks to many years. Treatment is correspondingly diverse, from `watchful waiting'' to high-dose chemotherapy with bone marrow stem cell transplantation. Cure is possible in an increasing number of patients and much interest currently lies in identifying patients with high-risk disease necessitating the use of intensive treatment regimens.


     

Lemierre's syndrome (necrobacillosis)

Lemierre''s syndrome or postanginal septicaemia (necrobacillosis) is caused by an acute oropharyngeal infection with secondary septic thrombophlebitis of the internal jugular vein and frequent metastatic infections. Fusobacterium necrophorum is the most common pathogen isolated from the patients. The interval between the oropharyngeal infection and the onset of the septicaemia is usually short. The most common sites of septic embolisms are the lungs and joints, and other locations can be affected. A high degree of clinical suspicion is needed to diagnose the syndrome. Computed tomography of the neck with contrast is the most useful study to detect internal jugular vein thrombosis. Treatment includes intravenous antibiotic therapy and drainage of septic foci. The role of anticoagulation is controversial. Ligation or excision of the internal jugular vein may be needed in some cases.


     

Intraoperative glove perforation—single versus double gloving in protection against skin contamination

Surgeons have the highest risk of contact with patients'' blood and body fluids, and breaches in gloving material may expose operating room staff to risk of infections. This prospective randomised study was done to assess the effectiveness of the practice of double gloving compared with single gloving in decreasing finger contamination during surgery.
In 66 consecutive surgical procedures studied, preoperative skin abrasions were detected on the hands of 17.4% of the surgeons. In the double gloving pattern, 32 glove perforations were observed, of which 22 were in the outer glove and 10 in the inner glove. Only four outer glove perforations had matching inner glove perforations, thus indicating that in 82% of cases when the outer glove is perforated the inner glove will protect the surgeon''s hand from contamination. The presence of visible skin contamination was also higher in perforation with the single gloving pattern (42.1%) than with the double gloving pattern (22.7%).
An overwhelming majority of glove perforations (83.3%) went unnoticed. Double gloving was accepted by the majority of surgeons, especially with repeated use. It is recommended that double gloves are used routinely in all surgical procedures in view of the significantly higher protection it provides.


     

Determinants for the course of acute sinusitis in adult general practice patients

BACKGROUND—Although the prognosis of acute sinusitis is important, little is known about it and the factors predicting its course in a general practice population.
OBJECTIVE—To determine the course of acute sinusitis and factors predicting it in adults in general practice.
METHODS—The prognostic value of demographic and clinical factors and the patient''s emotional state, for example anxious or depressed, were determined prospectively by means of multivariate analysis.
MAIN OUTCOME MEASUREMENTS—Resolution of facial pain, resumption of daily activities, and the patient''s reported improvement. Factors with a significant predictive value were used to classify the patients into three different groups: quick, moderate, and slow recovery.
RESULTS—The median time from enrolment to recovery was six (range percentile 25-75: 4-10) days in a population of 177 patients. Factors predictive of a prolonged clinical course were: female sex (hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.42 to 0.83), history longer than 14 days before inclusion (HR 0.62; 95% CI 0.41 to 0.94), headache, cold, or cough as a reason for the encounter (HR 0.65; 95% CI 0.44 to 0.96), and absence of cervical adenopathy (HR 0.71; 95% CI 0.51 to 0.96). Antibiotic treatment did not influence the course of disease. The median time to recovery was three days for patients with a quick, five days for those with a moderate, and seven days for those with a slow recovery.
CONCLUSION—In general practice acute sinusitis is mostly a self limiting disease. A limited number of characteristics are predictive of a (slightly) prolonged clinical course of acute sinusitis in general practice.


     

What is the prevalence of rheumatic disorders in general medical inpatients?

It has been suggested that rheumatological disorders are underdiagnosed in patients with medical problems and that this might be rectified by incorporating a standard brief screening examination as part of the routine assessment of all patients admitted to hospital with medical conditions. Therefore the GALS screening examination was used to assess the prevalence of rheumatic disease in 100 patients admitted with acute medical problems and in a further 100 in the rehabilitative phase of their disease. The nature of locomotor dysfunction in all patients with a positive result was defined by an independent review and then sensitivity and specificity of the screening test was calculated for rheumatic disease in both populations.
The median age of the two populations were 63 and 78 years respectively, with more females in the rehabilitation group. The overall prevalence of a positive screening test was 53% in the acute and 94% in the chronic disease groups, although the false positive rate in the rehabilitation patients was 30% due to factors other than rheumatic disorders limiting locomotor function (mainly orthopaedic and neurological conditions). The diagnosis of a rheumatological disorder was made de novo in a significant minority (10%) of patients and was usually amenable to treatment. The commonest rheumatic disorder was osteoarthritis which accounted for 55% of all rheumatic disease, followed by inflammatory joint disease (16%), and osteoporosis (12%). In addition to osteoporosis, Paget''s disease of bone and polymyalgia rheumatica were found more frequently in those patients undergoing rehabilitation than in those admitted with an acute medical problem. A number of clinically important associations between medical and rheumatic disorders were found, such as stroke disease with shoulder capsulitis and heart failure with gout.
The sensitivity of the GALS screening test was extremely high (92% and 100%), while its specificity fell in the rehabilitation group from 83% to 17%. None the less, it is felt that this study indicates that the routine use of this test should be considered as part of the assessment of all hospitalised patients with medical problems, whether acute or chronic.


     

Good prognosis in thyroid cancer found incidentally at surgery for thyrotoxicosis

An analysis of the outcome of thyroid carcinoma incidentally discovered in patients undergoing surgery for hyperthyroidism is presented. Among 986 patients with differentiated thyroid cancer, 23 had presented with symptoms and signs of hyperthyroidism. Graves'' disease was diagnosed in 11, multinodular goitre in eight and toxic adenoma in four. Following thyroidectomy, histology revealed papillary (18), follicular (four) and Hurthle cell (one) carcinoma. Tumour size ranged from 4 mm to 5.5 cm, multifocality was detected in three patients, and lymph node involvement in one. Two patients (one with associated Graves'' disease, one with multinodular goitre) relapsed locally and required further surgery; one developed distant metastases and died 7 years after initial presentation. Two patients died of unrelated causes; the remaining 20 patients are alive and well with a median follow-up of 16 (1-34) years. Differentiated thyroid cancer found incidentally at surgery for hyperthyroidism has a good prognosis.


     

The effect of passive smoking on pulmonary function during childhood

Passive smoking, especially of maternal origin, is known to influence adversely the development of children''s pulmonary function. In this study, the effect of parental smoking on the pulmonary function of 360 primary school children aged 9-13 (mean 10.8±0.7) years was investigated. Information on parental smoking history was collected using a questionnaire, and spirometric measurements were performed on the children.
All spirometric indices were lower in children who had been passively exposed to parental tobacco smoke than those not exposed. The percentage of households in which at least one parent smoked was 81.5%. This figure was significantly lower for mothers (27.5%) than for fathers (79%). Paternal smoking was associated with reduced levels of forced expiratory flow between 25-75% of vital capacity, peak expiratory flow, and flow rates after 50% and 75% of vital capacity expired (p<0.05). Maternal smoking did not have statistically significant adverse effects on children''s pulmonary function. This result might be due to the low occurrence of either pre- or post-natal smoking among mothers and confirms that, in our population, the main target group for anti-tobacco campaigns should be fathers.


     

The pathophysiological and molecular basis of Bartter's and Gitelman's syndromes

Molecular defects affecting the transport of sodium, potassium and chloride in the nephron through the ROMK K⁺ channel, Na⁺/K⁺/2Cl^- cotransporter, the Na⁺/Cl^- cotransporter and chloride channel have been identified in patients with Bartter''s and Gitelman''s syndromes. Defects of the angiotensin II type I receptor and CFTR have also being described. These defects are simple (ie, most are single amino acid substitutions) but affect key elements in tubular transport. The simplicity of the genetic defects may explain why the inheritance of these conditions remains unclear in most kindreds (ie, not just recessive or dominant) and emphasises the crucial importance of the conformational structure of these channels. Application of this molecular information will allow the early genetic identification of patients with these syndromes and enable us to differentiate between the various disorders at a functional level. It may also identify a sub-group in which the heterozygous form may make patients potentially exquisitely sensitive to diuretics.


     

Delays by patients in seeking treatment for acute chest pain: implications for achieving earlier thrombolysis

A study was set up to identify why patients delay seeking medical assistance after myocardial infarction. The study was performed in 100 consecutive patients with suspected acute myocardial infarction admitted to either the University Hospital of Wales, Cardiff, UK, or the Royal Jubilee Hospital, Victoria, British Columbia, Canada (50 patients from each centre). The main outcome measure was the delay from the onset of symptoms to admission to hospital. The mean total delay before admission was 385 minutes (SEM 45). The mean delay incurred by the patient in seeking assistance was 172 minutes (SEM 27), representing 45% of the total. Delay was longer in patients with crescendo angina and shorter in those later confirmed to have myocardial infarction. Patients with prior ischaemic heart disease (74% of patients) presented later than those with no such history. No other demographic or clinical factors predicted early or late presentation.
Delays in seeking medical assistance after the onset of severe chest pain contribute significantly to total delays in patients'' hospital admission and thrombolysis. The unexpected observation that patients with known ischaemic heart disease delay longer before seeking help in spite of their frequent contact with doctors, suggests that opportunities for educating patients are being wasted. Major efforts are needed to understand and modify behaviour of patients with chest pain to further reduce delays in treatment.


     

Evaluation of renal function in elderly heart failure patients on ACE inhibitors

A total of 187 heart failure patients aged 65-92 years, with pretreatment serum creatinine levels below 200 µmol/l, were monitored for more than 12 months on angiotensin-converting enzyme (ACE) inhibitor therapy. Optimal ACE inhibitor dosage was found in 27% of patients, while a significant deterioration in renal function, characterised by >20% increase in serum creatinine to >200 µmol/l, occurred in 25 patients. This was most closely attributable to ACE inhibitor treatment per se (implying co-existence of bilateral renal artery stenosis) in only four cases, including one in whom renal deterioration was reproducible on inadvertent rechallenge. In the other 21, renal deterioration was attributable to diuretic-related blood volume depletion (two cases), nonsteroidal anti-inflammatory drugs (two cases), obstructive uropathy (two cases), preterminal renal shutdown (two cases), and the interaction between diuretic and ACE inhibitor dosage (including long-acting vs short-acting drugs) (13 cases). This study could serve as the basis for future comparisons of ACE-inhibitor-related renal deterioration when the entry requirement is optimal ACE inhibitor dosage.


     

The Natural Progression of Parkinson's Disease in a Small Cohort with 15 Drug-na?ve Patients

Background:

The studies of the natural progression of Parkinson''s disease (PD) in Chinese populations have been lacking. To address this issue and obtain a preliminary data, we conducted a PD progression assessment in 15 adults with de novo PD from a nutritional intervention trial (NIT) cohort in Lin County China.

Methods:

Using the Copiah County screening questionnaire and United Kingdom Parkinson''s Disease Society Brain Bank diagnostic criteria, we surveyed the available NIT cohort members in 2000 and diagnosed 86 patients as PD. In 2010, we resurveyed all PD patients and confirmed definite PD diagnosis in 15 cases with the rest of them being dead (54); having probable (10) PD or vascular Parkinsonism (3); refusing to participate (2); or being away (2). In both surveys, we used Hoehn and Yahr (HY) scale and assessed the disease progression. Unified Parkinson''s Disease Rating Scale (UPDRS) was added to the second survey.

Results:

In 2010, the average disease duration for 15 definite PD patients was 13.6 ± 7.3 years. Over a 10-year time span, 9 out of 15 patients remained at the same HY stage while the remaining 6 progressed. Rigidity (47% vs. 100%; P = 0.002) and postural instability (7% vs. 47%; P = 0.005) worsened significantly. The mean UPDRS motor scores in 2010 were 39.4 ± 23.7.

Conclusions:

Overall worsening of motor function in PD seems to be the rule in this untreated cohort, and their rate of progression seemed to be slower than those reported in the western populations.     

Permanent pacemaker insertion in a district general hospital: indications, patient characteristics, and complications

This report reviews the experience of permanent pacemaker insertion in a district general hospital (catchment population of 350 000) and makes a comparison with the national database and other hospitals in the UK.
METHODS—The records of all patients receiving a permanent pacemaker in the inclusive period January 1996 to December 1998 were reviewed. Data collected included number of patients paced each year, age, sex, indications, and complications.
RESULTS—In the three years reviewed 200 patients received new permanent pacemakers, a rate of 190 per million population per year, which is similar to the national implantation rate of permanent pacemakers but lower than that of most European countries (see discussion). The majority of patients paced were elderly (75% were above the age of 70 years).
Atrioventricular block (including complete heart block, 45%, and Mobitz type 2 block, 12.5%) was the commonest indication for permanent pacemaker insertion, followed by sick sinus syndrome (25%) and these findings are comparable to those reported previously. However, carotid sinus syndrome was responsible for 16% of the patients paced and this was higher than that reported in the national database (6.5%). Only 1% of the pacemaker modes used was inappropriate and the complication rate was low at 3%.
CONCLUSIONS—This report confirms that permanent pacemaker insertion can be effectively and safely provided locally for the increasingly ageing population. The implantation rate both locally and nationally is still much lower than that of some countries in Europe.


     

Evolution of insulin resistance in coronary artery disease patients on four different pharmacological therapies

The objective of the study was to examine the evolution of insulin sensitivity in a group of patients with stable coronary artery disease receiving one of four different pharmacological therapies. Insulin sensitivity was evaluated using an insulin suppression test in 40 newly diagnosed patients with coronary artery disease and no previous history of metabolic disorders, who were not taking any medication which might affect insulin sensitivity. The insulin suppression test consisted of a constant infusion of glucose, insulin and somatostatin for 150 min; insulin resistance was estimated by determining the steady-state plasma glucose concentrations during the last 60 minutes of the test. The insulin sensitivity index was calculated by the formula: insulin sensitivity index = (glucose infusion rate/steady state plasma glucose concentrations) × 10³. A second insulin suppression test was performed after 6 months'' therapy with either isosorbide mononitrate, atenolol, diltiazem or captopril in 30 of the 40 patients.
  There were no differences between any of the groups before therapy was initiated. After 6 months, patients treated with captopril and, to a lesser extent, those treated with diltiazem showed statistically significantly decreased steady state plasma glucose concentrations and increased insulin sensitivity index compared to basal values. No statistically significant differences were found in the other two groups. We conclude that captopril and, to a lesser extent, diltiazem improve insulin sensitivity in patients with stable coronary artery disease.


     

Prognostic value of stress echocardiography in women with high (> or = 80%) probability of coronary artery disease

OBJECTIVE—To assess the prognostic significance of stress echocardiography in women with a high probability of coronary artery disease (CAD).
SETTING—Secondary and tertiary cardiology unit at a university teaching hospital.
PARTICIPANTS—A total of 135 women (mean (SD) age 63 (9) years) with pre-test probability of CAD ⩾80% were selected from a database of patients investigated by treadmill or dobutamine stress echocardiography between 1995 and 1998.
MAIN OUTCOME MEASURES—Patients were followed up for occurrence of subsequent cardiac events (cardiac death, myocardial infarction, admission with unstable angina, and revascularisation) using a structured telephone interview and case note review.
RESULTS—Each patient had between two and seven (mean 3.5) CAD risk factors and pre-test probability of CAD ⩾80%. Ninety three patients (68.9%) had negative stress echocardiography. Mean (SD) follow up was 20.1 (8.5) months. There were six events in the positive stress echocardiography group (two cardiac deaths, one unstable angina, three revascularisations), and one event in the negative stress echocardiography group. Cox regression analysis showed positive stress echocardiography (p=0.02) and age (p=0.03) to be the only univariate predictors and positive stress echocardiography to be the only independent predictor of future cardiac events (relative risk 8.9, confidence interval 1.0 to 76.5, p=0.04). Cumulative event free survival to 38 months was 98% in the negative stress echocardiography and 50.7% in the positive stress echocardiography groups.
CONCLUSION—In women with high pre-test likelihood of CAD: (1) negative stress echocardiography identifies a subgroup with low risk of cardiac events who do not require further invasive investigation and (2) positive stress echocardiography identifies a subgroup with increased risk of subsequent cardiac events.


     

Guillain-Barr�� syndrome as an extraintestinal manifestation of Crohn's disease.

A variety of extraintestinal manifestations, probably immune-mediated, may appear during relapses of Crohn''s disease. We report the clinical observation of a 34-year-old woman who developed a Guillain-Barré syndrome, aphthous stomatitis and oligoarthritis during a relapse of Crohn''s ileocolitis. This case suggests that the Guillain-Barré syndrome may be another extraintestinal manifestation of Crohn''s disease.     

Silent myocardial ischaemia in patients with proved coronary artery disease: a comparison of diabetic and non-diabetic patients

OBJECTIVE—To determine whether diabetic patients with coronary artery disease are more likely to experience silent myocardial ischaemia than subjects without diabetes.
SUBJECTS—Patients undergoing coronary angiography at a regional cardiothoracic unit, identified as having diabetes from the local district diabetic register/database.
DESIGN—The coronary angiograms and exercise treadmill tests of 100 diabetic and 100 non-diabetic patients who all had significant coronary artery disease and maximal effort exercise tests were reviewed. Patients were individually matched for age group, gender, severity of coronary artery disease, and indication for treadmill test.
OUTCOME MEASURES—Significant coronary artery disease was defined as a stenosis of greater than 50% diameter in at least one of the major coronary artery segments. Exercise tests were graded as positive if the electrocardiographic (ECG) recording showed planar or downsloping ST segment depression of ⩾1 mm in more than two leads at 80 ms post J-point or if there was a blood pressure fall ⩾10 mm Hg after an initial rise. A negative exercise test was defined as one in which the subject experienced no pain, had no ECG changes after maximal effort and had a normal blood pressure response. Subjects who did not experience any form of typical angina-type pain during a positive exercise test were defined as having an episode of silent ischaemia. Patients with symptomatic ischaemia were those who experienced typical angina-type pain with accompanying ST segment changes. Patients with a negative exercise test were defined as having "undetermined ischaemia". This category included all those without ECG evidence of myocardial ischaemia during the exercise test (with or without accompanying chest pain).
RESULTS—In the diabetic patients, 34% had ECG evidence of silent ischaemia on treadmill testing compared with only 19% of the non-diabetic controls (p<0.02).
CONCLUSIONS—This study shows that diabetic patients with proved coronary artery disease have a higher risk of developing silent myocardial ischaemia during exercise than non-diabetic patients.


     

Utility of glomerular morphometry in diagnosing pediatric renal disease

BackgroundMorphometry has now become a useful adjunct to the diagnostic armamentarium of light, immunofluorescence, and electron microscopy, as it provides a deep insight into quantitative parameters of nephropathies. There has been a limited study on its utility especially in diagnosing pediatric renal diseases. This study is probably the first in India to assess the contribution of this diagnostic modality in pediatric renal disease to the best of authors’ knowledge.MethodsIt''s a retrospective cross-sectional study covering a period of 05 years at a tertiary care hospital. The study includes 28 cases of pediatric (age till 14 years) nephropathies. The diseases were divided into two groups—nephrotic presentation and nephritic presentation. Glomerular morphometry was performed and mean was calculated for Bowman''s capsule area, glomerular capillary tuft area, and Bowman''s space area; for the three groups, respectively. Renal parameters serum creatinine, blood urea, 24 h urine protein were studied along with hemoglobin and serum cholesterol for the cases. Data were analyzed using SPSS software, version 25, for one-way ANOVA comparing mean in the three groups.ResultsWe found a positive and significant correlation between Bowman''s capsule area with proteinuria, blood urea, and serum creatinine. There was positive and significant correlation between glomerular capillary tuft area and serum creatinine and Bowman''s space area and proteinuria in both the groups.ConclusionGlomerular morphometry may contribute to the diagnosis of some glomerulopathies and the association between glomerular morphometric parameters and laboratory data may promote better understanding of the prognosis of these patients.     

Gallstones and cholecystectomy in modern Britain

BACKGROUND—It has been suggested that gallstone disease is now commoner, and that this might explain an increase in cholecystectomy rates, though conclusive evidence has been lacking.
METHODS—All the non-forensic necropsy results for Dundee 1953-98 were examined to assess the prevalence of gallstone disease. The NHS Scotland annual cholecystectomy figures were extracted from their earliest availability in 1961 up to the present. The subgroup of patients from Dundee was analysed separately, as were laparoscopic procedures, which were recorded from 1991.
RESULTS—Gallstone disease was much commoner in 1974-98 than in 1953-73. Increasing age was the main determinant of gallstone disease. Though gallstone disease was commoner in women than men aged 40-89, there was no sex difference under 40 or over 90 years. Cholecystectomy became much commoner in the 1960s when frequency of gallstone disease did not change. It increased further in the 1970s, peaking in 1977-8. There was a gradual fall in rates in the 1980s when gallstone prevalence remained high. There was a further moderate rise in the 1990s after the wide introduction of laparoscopic cholecystectomy. Cholecystectomy is now much commoner in young women and this change started in the 1960s. By contrast, cholecystectomy in men has become more prevalent in the older age group.
CONCLUSIONS—Gallstones were definitely more common in both sexes at all ages over 40 in the last 25 years. Changes in the cholecystectomy rates are only partly explained by changes in gallstone prevalence, and are more determined by surgical practice.