SYSTEMIC LUPUS ERYTHEMATOSUS—Early Cytologic Diagnosis

The diagnosis of systemic lupus erythematosus—a relatively common disease—is difficult because of the variable nature of the symptoms, which resemble those of many other conditions. The finding of the characteristic cells is pathognomonic, although failure to find them does not rule out the diagnosis.If the diagnosis is suspected the “L.E.” cell test should be performed on two samples of blood from the veins and one from the bone marrow. After separation of a haparinized sample by centrifuge, a drop from the buffy coat is Wright-stained on a slide and examined for rouleaux formation and for a hematoxylinstaining material sometimes seen in intercellular bodies (which may be surrounded by a rosette of leukocytes) and sometimes seen as ingested by a leukocyte. Only the last finding is positively diagnostic of lupus erythematosus.A statistical analysis of 62 cases treated at the Los Angeles County General Hospital is given. Because of the frequency of rheumatoidlike arthritic changes in the disease, all patients with this form of arthritis should be given the test. Spontaneous remission and then relapse after a long asymptomatic interval occurred in many cases. With early diagnosis and vigorous treatment with cortisone and corticotropin, many patients can be relieved of symptoms.     

PSYCHOSIS AND SYSTEMIC LUPUS ERYTHEMATOSUS—A Review of the Literature and Case Reports

In a review of the literature of the last 60 years concerning the association between psychosis and systemic lupus erythematosus, reports of 227 cases of this association were found. The average incidence of psychosis in the various series of systemic lupus erythematosus that were reviewed was 22 per cent. In only 25 per cent of the cases in which the information was given was the psychosis associated with steroid therapy.The psychiatric manifestations are variable and may be associated with a neurological disorder. Psychosis may antedate by many years other features of lupus. The psychosis due to lupus may respond to steroid therapy. Since systemic lupus erythematosus sometimes may be an important differential diagnosis of functional psychosis, appropriate diagnostic studies should be carried out in psychotic patients who have an accelerated sedimentation rate or positive serological test for syphilis without apparent reason.     

The Spectrum of Extrapulmonary Tuberculosis

The incidence of new cases of extrapulmonary tuberculosis has remained constant, despite the decline in new cases of active pulmonary tuberculosis. This might be due to a delay in recognition, and particularly a lack of consideration of tuberculosis when the presenting symptoms are other than respiratory. Extrapulmonary tuberculosis should be considered in the differential diagnosis of bone, joint, genitourinary tract and central nervous system (CNS) diseases.To determine factors that might delay recognition and identification, 62 patients having extrapulmonary tuberculosis during 1969-1972 at the Los Angeles County-University of Southern California Medical Center were studied.Three quarters of these patients had had CNS, skeletal or genitourinary tuberculosis in equal distribution or 25 percent each. CNS involvement was seen frequently in the disseminated form. Presenting symptoms were protean and not specific, such as fever, anorexia, weight loss, cough, lymphadenopathy and neurologic abnormalities. Roentgenograms of the chest were abnormal in most. When a roentgenogram of the chest suggests pulmonary tuberculosis, signs and symptoms in other body systems should suggest extrapulmonary tuberculosis. If no abnormalities are seen on a roentgenogram of the chest, however, this does not preclude the diagnosis of extrapulmonary tuberculosis. Neither does a negative tuberculin skin test exclude the condition.Abnormal laboratory findings are common, especially in disseminated tuberculosis. These include various anemias, bone marrow disorders, hyponatremia due to inappropriate antidiuretic hormone syndrome. Analyses of pleural, peritoneal, pericardial and joint fluid usually show an exudate high in lymphocytes and occasionally low in glucose. Similar findings are seen in spinal fluid. The histological features of caseous or noncaseous granulomas are suggestive of but not specific for tuberculosis. Only culture of mycobacteria from sputum, urine, spinal fluid, pleural and other effusions and tissue biopsy specimens will yield a definitive diagnosis.Physicians must have a high index of suspicion to diagnose extrapulmonary tuberculosis, as it can resemble any disease in any organ system. Immediate therapy in the disseminated variety, sometimes even before a definite diagnosis can be made, may be lifesaving.     

T-zone lymphoma--clinical symptoms, therapy, and prognosis (author's transl)]

The clinical symptoms, response to therapy, and prognosis of T-zone lymphoma were analyzed in 32 cases. This recently defined lymphoma entity developed relatively quickly with generalized lymphadenopathy and general malaise. Hepatomegaly and/or splenomegaly and skin efflorescence were frequent presenting symptoms. A few patients showed hyperimmune reactions and occasionally severe autoimmune hemolytic anemia. The erythrocyte sedimentation rate was usually markedly elevated. There was sometimes a polyclonal increase in serum immunoglobulin, sometimes a reduction. Blood and bone marrow smears from a few patients showed occasional atypical lymphocytes. A remarkable finding was the frequent involvement of lung or pleura (40.5% of the patients). The prognosis is unfavorable. Most of the patients were in stages III or IV at the time of diagnosis. Massive infiltration of organs, resistance to routine therapy, and decreasing resistance to infection resulted in death soon after diagnosis. The probability of survival was 0.48 in the first year after diagnosis. The prognosis for patients in stages I and II was clearly better than that for patients in stages III and IV.     

Diagnosis of pseudomembranous colitis.

Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections not requiring operations; the other 22 cases all occurred after major surgery. All the patients had diarrhoea; six patients also had fever with clinical signs of sepsis, and three had abdominal pain thought to be due to anastomotic dehiscence after colonic resection. Pseudomembranous colitis was associated with white blood counts over 15 000/mm3 in 17 patients and albumin concentrations of less than 30 g/1 in 18. Pseudomembranous colitis was an incidental finding at necropsy in two of six patients who had not had an operation. Of the 22 patients who had had major surgery, nine died from this complication; in all except two of these cases the diagnosis was made only at necropsy. If pseudomembranous colitis is suspected on clinical grounds or if there is an unexplained complication after colorectal surgery repeat sigmoidoscopy and testing for faecal toxins should be carried out to establish the diagnosis so that prompt supportive treatment can be given.     

Diseases of the Skin: Drug Therapy of Urticaria

Most patients with urticaria can be assessed by taking a relatively simple history with few or no investigations and controlled by a suitable antihistamine given at appropriate times until spontaneous resolution occurs without a complete diagnosis ever being made. Those that do not respond in this way require sometimes quite elaborate investigations, the institution of which would be an imposition in a mild case. Even after full investigation and ringing the changes of all available drugs, too many cases persist to the frustration of all concerned.     

Inappropriate indication for surgical treatment of goiter diagnosed as hyperactive

Aim of this report is a stress of over-hasty classification to the surgical treatment of goiter diagnosed as hyperactive. The authors suppose that the cause of such errors is an incorrect interpretation of the current diagnostic tests, especially scintigraphy, and not very careful clinical evaluation of cases diagnosed as hyperthyroidism, being vegetative neurosis which is sometimes accompanied by the arterial blood hypertension. Examples of patients misclassified from the surgical treatment after proper diagnosis based on the clinical symptoms confirmed with thyroid gland diagnostic test are given. The authors stress that the detailed knowledge on the clinical course of hyperthyroidism and proper interpretation of the diagnostic tests help to avoid such errors.     

Acute lymphoblastic leukemia: a study of 25 cases by scanning electron microscopy.

Cells from 25 cases of acute lymphoblastic leukemia (ALL) were studied under the scanning electron microscope (SEM). In 24 of the cases, the vast majority of circulating leukaemic cells had few microvilli. Villous cells were rarely encountered and prominent ridge-like profiles and ruffled membranes were not seen. Only six cases were studied by immunological techniques and four of the cases were of the null type while in two the cells bore detectable T-markers. It seems that ALL is almost always associated with the presence of cells with few microvilli in the peripheral circulation, differing in this respect from most cases of CLL. Although circulating leukaemic lymphocytes with few microvilli are sometimes seen in CLL, the most frequent cell type encountered is a more villous lymphocyte. Differences between leukaemic cells from patients with ALL, CLL and non-lymphoblastic leukaemias are discussed. It appears that SEM may help to distinguish lymphoblastic and nonlymphoblastic leukaemic cells in many instances and can be used as a useful adjunct to other modes of microscopy in the diagnosis of acute leukaemia.     

Hyperprolactinemia: causes, diagnosis, and treatment

The basic data on hyperprolactinemia (i.e. an excess of PRL above a reference laboratory's upper limits), the most common endocrine disorder of the hypothalamic-pituitary axis are given in this review. The following issues are discussed: regulation of prolactin (Prl) secretion, definition of hyperprolactinemia, its etiology and pathogenesis as well as its symptoms, diagnosis, and treatment (including medical and surgical therapy). It should be stressed that finding of elevated PRL serum concentrations constitute the beginning of diagnostic procedure and, after exclusion of physiologic, pharmacologic, and other organic causes of increased PRL levels, should be followed by detailed diagnosis including MRI. In patients in whom hyperprolactinemia has been confirmed the treatment with dopamine agonists (with prevalence of cabergoline, followed by quinagoline) is currently considered first-choice therapy. Surgery should be performed only in the patients resistant or intolerant to these agents, or in patients who refuse long-term therapy.     

Clinical and anorectal motility features in chronically constipated children

Constipation is a common problem in children. It can be a symptom of functional disorder in majority of cases, but sometimes a serious organic disease is a cause of constipation. Anorectal manometry plays an important role in the diagnostic procedure. It can be presumed that some values of manometric parameters could be very useful in treatment plan. The aim of this study was to confirm or exclude such limits in manometric finding, to make a plan of the therapy more accurate. Therefore the group of 81 constipated children was investigated. There were 58 patients suffering from functional constipation and 23 with organic disorders. The age of the patients was 3 to 15 years. Scoring system was applied to estimate severity of constipation and anorectal manometry was performed. Our results did not show significant correlation between clinical symptoms and signs and the values that we obtained using anorectal manometry. But, we recommend anorectal manometry because it is a safe method and contributes to clarify the diagnosis, which is very important for treatment plan.     

Cerebral vascular occlusion; angiographic diagnosis

Cerebral arterial occlusion is a fairly frequent condition. We have diagnosed nine cases by cerebroangiography in the past two years, and there are many patients not given this special examination.Precise diagnosis has become more important as advances in therapy make prognosis more hopeful. The symptoms are various according to the location and degree of occlusion and the amount of collateral circulation.Angiographic diagnosis is not difficult, but repeated demonstration of the block should be insisted on. This is best done with multiple exposures after a single injection of contrast medium. We use 7 cc. of 50 per cent Hypaque(R) and one exposure per second through the arterial, capillary and venous phases. The films should cover the entire head and neck lest an occlusion in the common carotid be overlooked. We have found the Schonander biplane apparatus very satisfactory, using films 14 inches square and exposing them in anteroposterior and lateral projections simultaneously.     

Malaria in Birmingham and a London teaching hospital.

During the past five years the incidence of imported malaria increased among patients seen in East Birmingham Hospital and in St Thomas''s Hospital, London. Plasmodium vivax was the predominant species in Birmingham, and was almost always acquired by Asian immigrants visiting the Indian subcontinent. In St Thomas''s P falciparum was most commonly imported, usually by African immigrants visiting Nigeria and Ghana. Two patients (one Irish, one Japanese) died of falciparum malaria after visiting tropical Africa. In both hospitals the immigrant patients had seldom taken prophylactic drugs, and the few who had, ceased to do so on arrival in the UK and sometimes before leaving the malarious country. Apparently immigrants who visit their homeland do not consult their general practitioners before travelling, are given inappropriate advice, or do not take appropriate advice when given. Since the incidence of imported falciparum malaria in the UK is rising, the following points should be considered: the infection may be lethal, particularly in patients lacking immunity; it can mimic other diseases, which may lead to delayed diagnosis; severe disease may be associated with few parasites on a blood film, and even if the result is negative further tests should be performed; clinicians and hospital pharmacists should be aware of the need to keep permanent stocks of parenteral chloroquine and quinine preparations.     

A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome

The underlying basis of many forms of syndromic craniosynostosis has been defined on a molecular level. However, many patients with familial or sporadic craniosynostosis do not have the classical findings of those craniosynostosis syndromes. Here we present 61 individuals from 20 unrelated families where coronal synostosis is due to an amino acid substitution (Pro250Arg) that results from a single point mutation in the fibroblast growth factor receptor 3 gene on chromosome 4p. In this instance, a new clinical syndrome is being defined on the basis of the molecular finding. In addition to the skull findings, some patients had abnormalities on radiographs of hands and feet, including thimble-like middle phalanges, coned epiphyses, and carpal and tarsal fusions. Brachydactyly was seen in some cases; none had clinically significant syndactyly or deviation of the great toe. Sensorineural hearing loss was present in some, and developmental delay was seen in a minority. While the radiological findings of hands and feet can be very helpful in diagnosing this syndrome, it is not in all cases clearly distinguishable on a clinical basis from other craniosynostosis syndromes. Therefore, this mutation should be tested for in patients with coronal synostosis.     

Neonatal Necrotizing Enterocolitis: Clinical and Radiological Features

Necrotizing enterocolitis is an uncommon but dangerous disease in premature infants. Ten cases, seen over a three-year period at the Stanford University Medical Center, represented an incidence of 0.4 percent. The patients, six of whom died, derived from a general population, in contrast to the large series of patients reported in the literature in which the incidence was from 0.9 percent to 3.7 percent.^3-6The initial symptoms—rapid respiration, periodic breathing, lethargy and irritability—were identical to those which occurred in numerous infants who had respiratory disease. Subsequent symptoms (abdominal distension, in 100 percent; vomiting, 80 percent; apneic spells, 70 percent; jaundice, 70 percent; guaic-positive stools, 60 percent) were those of nonspecific acute abdominal disease.The radiologist first made the diagnosis in 90 percent of cases. Interstitial air in the wall of the gut and the retroperitoneum, and portal vein gas were the most diagnostic radiographic features. Barium contrast studies were not helpful, and in one case led to the erroneous diagnosis of small bowel volvulus.Plain abdominal radiographs must be taken of all premature infants with symptoms of nonspecific acute abdominal disease. If the radiographs are negative, but symptoms continue, they should be repeated at frequent intervals, for early diagnosis is critical to institution of proper therapy.     

An immunocytochemical approach to detection of mitochondrial disorders.

Mitochondrial disorders can lead to a confusing array of symptoms, which frequently makes a diagnosis difficult. Traditional approaches to such diagnoses are based on enzyme activity assays, with further characterization provided by genetic analysis. However, these methods require relatively large sample sizes, are time-consuming, labor-intensive, and show variability between laboratories. Here, we report an immunocytochemical test that makes use of monoclonal antibodies to subunits from each of the oxidative phosphorylation complexes and pyruvate dehydrogenase to aid in the detection of mitochondrial disorders. It can be completed and data analyzed in less than 4 hr. We have used this test to study fibroblast cultures from patients with mitochondrial disorders arising from both mitochondrial DNA and nuclear DNA defects. We have also examined cases of Leigh syndrome arising from different genetic causes. We show that patients can be categorized on the basis of which complexes are affected and whether or not the defect being studied shows a mosaic distribution, an indicator of whether the causal mutation(s) is/are in the mitochondrial or nuclear genome. Immunocytochemical analysis as described here should be considered as an initial screen for mitochondrial disorders by which to direct (and limit) the subsequent enzymatic and genetic tests required to make an unambiguous diagnosis.     

THE ERECT LATERAL LUMBAR ROENTGENOGRAM IN THE EVALUATION OF “LOW BACK” PAIN

A study was made of the potential value of the erect lateral flexion lumbar roentgenogram in a series of 50 adults, some with symptoms of low back pain and some without such symptoms. The film was made in addition to the standard antero-posterior, lateral and sometimes oblique views taken in the recumbent position.In 11 of 37 patients with low back pain, some narrowing of lumbar discs was visible in both horizontal and erect lateral films, the degree being not significantly different between the two positions. In one patient, localized anterior narrowing of a lumbar disc, which was not visible in the recumbent lateral film, was observed. This finding was confirmed at a subsequent examination.In one of 13 patients without lumbar area symptoms, slight anterior narrowing of a lumbar disc could be seen in the erect lateral film but not in the horizontal. The reason for this is not known; it may be physiologic in this particular patient.The value of the routine erect lateral flexion lumbar roentgenogram was not confirmed by this preliminary study.     

The Extrarenal Manifestations of Hypernephroma

The extrarenal manifestations of hypernephroma in 34 medical patients are described, and the literature on this subject is reviewed. One case presented with hematuria and 11 other cases with metastases. Presentation was not obviously related to metastases in 22 patients. Eight were first seen because of fever or general weakness. Vascular disturbances in six included hypertension, thrombophlebitis, inferior vena caval obstruction and varicocele. Four patients had gastrointestinal complaints; one had hypercalcemia and another musculoskeletal symptoms. Two cases had neurological syndromes, one of which proved to be due to metastases. The overall incidence of systemic features was greater and included anemia, eosinophilia, a leukemoid reaction and thrombocytosis. Polycythemia, amyloidosis and hyponatremia were not encountered. Urographic procedures were performed in half of the patients, most of whom had an abdominal mass. Calcium was visible radiologically in the tumour in five cases. The diagnosis was not made in 19 and was an unexpected finding at autopsy in 10. Appreciation of the extrarenal manifestations of hypernephroma might lead to earlier diagnosis.     

Routine diagnosis of herpes simplex virus (HSV) encephalitis by an internal DNA controlled HSV PCR and an IgG-capture assay for intrathecal synthesis of HSV antibodies

Background: The development of antiviral therapy increases the need for rapid, sensitive and reliable methods or combination of methods for diagnosis and monitoring herpes simplex encephalitis, HSE.Objectives: Evaluation of diagnostic performance of three successively developed HSV PCR assays when combined with a new capture ELISA for HSV intrathecal antibody production (ITT).Study design: During a 3.6 year period a total of 4.206 CSF and serum samples from about 4.140 hospitalized patients with a tentative diagnosis of HSE were analyzed by a new ELISA for ITT. 1.962 CSF samples were examined also by PCR. Clinical signs and symptoms and additional tests were obtained on all ITT and/or PCR positive patients. In 1993 the PCR was a double PCR. In 1994 the PCR was a single PCR with internal inhibition control. Positive samples were confirmed by a different confirmative PCR to increase the specificity. From 1995 the PCR was as in 1994 but samples were no longer divided in the serology routine laboratory.Results: A total of 33 HSE cases was found (incidence 1.8 HSE per million people). All patients were treated with aciclovir. Three patients died, 9 patients had primary infection, 2 patients had HSE previously, and 2 patients relapsed. Only 11 patients recovered satisfactory. Of all 37 positive ITT 7 were unlikely positive. False positive PCR was seen in 1993 and 1994, due to sample-to-sample contamination during division of samples, but was not seen since 1995 when this procedure was changed. The test results depended on the state of the disease. Thus, the sensitivity, specificity, PPV and NPV for ITT were highest when performed more than 1 week after debut of symptoms whereas these values were highest using PCR within the first week.Conclusion: Routine PCR diagnosis of HSE type 1 and 2 is a highly sensitive and specific method that should be performed together with serological ITT to cover the whole time span from debut of symptoms to several weeks after hospitalization.     

Trimethylaminuria: causes and diagnosis of a socially distressing condition

Trimethylaminuria is a disorder in which the volatile, fish-smelling compound, trimethylamine (TMA) accumulates and is excreted in the urine, but is also found in the sweat and breath of these patients. Because many patients have associated body odours or halitosis, trimethylaminuria sufferers can meet serious difficulties in a social context, leading to other problems such as isolation and depression. TMA is formed by bacteria in the mammalian gut from reduction of compounds such as trimethylamine-N-oxide (TMAO) and choline. Primary trimethylaminuria sufferers have an inherited enzyme deficiency where TMA is not efficiently converted to the non-odorous TMAO in the liver. Secondary causes of trimethylaminuria have been described, sometimes accompanied by genetic variations. Diagnosis of trimethylaminuria requires the measurement of TMA and TMAO in urine, which should be collected after a high substrate meal in milder or intermittent cases, most simply, a marine-fish meal. The symptoms of trimethylaminuria can be improved by changes in the diet to avoid precursors, in particular TMAO which is found in high concentrations in marine fish. Treatment with antibiotics to control bacteria in the gut, or activated charcoal to sequester TMA, may also be beneficial.     

Irritable bowel syndrome: a review on the role of intestinal protozoa and the importance of their detection and diagnosis

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which abdominal pain is associated with a defect or a change in bowel habits. Gut inflammation is one of the proposed mechanisms of pathogenesis. Recent studies have described a possible role for protozoan parasites, such as Blastocystis hominis and Dientamoeba fragilis, in the etiology of IBS. Dientamoeba fragilis is known to cause IBS-like symptoms and has a propensity to cause chronic infections but its diagnosis relies on microscopy of stained smears, which many laboratories do not perform, thereby leading to the misdiagnosis of dientamoebiasis as IBS. The role of B. hominis as an etiological agent of IBS is inconclusive, due to contradictory reports and the controversial nature of B. hominis as a human pathogen. Although Entamoeba histolytica infections occur predominately in developing regions of the world, clinical diagnosis of amebiasis is often difficult because symptoms of patients with IBS may closely mimic those patients with non-dysenteric amoebic colitis. Clinical manifestations of Giardia intestinalis infection also vary from asymptomatic carriage to acute and chronic diarrhoea with abdominal pain. These IBS-like symptoms can be continuous, intermittent, sporadic or recurrent, sometimes lasting years without correct diagnosis. It is essential that all patients with IBS undergo routine parasitological investigations in order to rule out the presence of protozoan parasites as the causative agents of the clinical signs.