Goiter in Tibetan Medicine

The visit of two Tibetan physicians provided a unique opportunity to gain insight into a practice of medicine very different from that of Western civilization. Initial discussions indicated that the practice of medicine and mysticism were inextricably interwoven in the Tibetan culture. Accordingly, the focus of the study was directed to goiter, which is both common in the Himalayas and easy to define.In Tibetan medical practice, illness is considered to be derived from both proximate and distant causes. Three humors, “wind,” “bile,” and “phlegm” are thought to be responsible for normal mental and physical functions when in balance, but disease when out of balance. Goiter was thought to be due to an imbalance of these humors. The Western discovery that endemic goiter in the Himalayas was due to iodine deficiency explained the proximate cause but did not explain why some individuals have goiter and others do not in the same iodine deficient village.     

INTERSTITIAL CYSTITIS

Interstitial cystitis, a disease of unknown origin which occurs predominantly in women, causes great pain and considerable disability. In most cases, the long interval between onset of symptoms and establishment of the diagnosis is due to a lack of familiarity with the disease.Although there is no “cure,” several forms of therapy may lead to improvement. In a series of 27 patients, 15 received benefit from distention of the bladder through the use of a solution of monoxychlorosene.     

Thalassaemia in the British

Different forms of thalassaemia or related disorders were found in 116 people of apparently pure British stock. Among them were one family with a child homozygous for β-thalassaemia and eight heterozygous relatives, 16 families with 83 persons heterozygous for β-thalassaemia, two families with three persons with Hb H disease and three heterozygous for α-thalassaemia 1, one family with a child apparently homozygous for the “silent β-thalassaemia gene,” one family with six members heterozygous for a form of β-thalassaemia intermedia, and three families with 11 members heterozygous for different types of hereditary persistence of fetal haemoglobin. The clinical, haematological, and haemoglobin biosynthetic findings in these persons were similar to those of patients with thalassaemia from other racial groups. The heterozygous state for β-thalassaemia is overlooked in British patients, particularly during pregnancy, because it is not considered in the differential diagnosis of refractory anaemia. In many cases this leads to much unnecessary investigation and potentially harmful treatment.There seem to be several varieties of hereditary persistence of fetal haemoglobin production among British people. These conditions, while not causing anaemia, may cause difficulties during examination of maternal blood for fetal cells and may, if inherited with a β-thalassaemia gene, produce an unusually high level of Hb F in a person heterozygous for β-thalassaemia.     

Psychiatric assessment of patients with “20th-century disease” (“total allergy syndrome”)

“Twentieth-century disease”, or “total allergy syndrome”, is a condition attributed to hypersensitivity to the environment that may sometimes be seen as so serious that the patient is incapable of living in the modern world. Although the popular media frequently carry stories about it, there is little scientific literature. It is diagnosed by clinical ecologists, who maintain, among other theories, that susceptible individuals experience an overload in assaults by artificial materials in the environment. The patients usually have multiple ill defined symptoms for which no organic cause can be found, but they vigorously resist psychiatric referral, as they attribute their symptoms to allergy. A group of 18 patients who were purportedly suffering from 20th-century disease were referred to a university psychiatric consultation liaison service. They virtually all had a long history of visits to physicians, and their symptoms were characteristic of several well known psychiatric disorders. The case histories and management of three of them are presented. Although this group of patients may have been atypical in that they had more severe psychologic symptoms, the experience indicates that a psychiatric diagnosis ought to be considered. The symptoms of 20th-century disease have much in common with other conditions known to physicians for centuries.     

Pulmonary Alveolar Proteinosis—Review of the Literature with Follow-up Studies and Report of Two New Cases

In the period from 1958, when Rosen and coworkers first reported a condition in which the pulmonary alveoli are filled with an eosinophilic material, to the beginning of 1964, reports of 93 cases had accumulated in the world literature, including two cases included herein. The cause of this disease, which Rosen called “pulmonary alveolar proteinosis,” is not known, nor is there a known means of cure.The usual patient is a white man between 30 and 50 years of age who may do any kind of work. The first symptoms may be those of pulmonary infection or pulmonary insufficiency. Patients with pulmonary alveolar proteinosis are prone to nocardiosis and infection with other fungi. Diagnosis is made by lung biopsy.Twenty of the 93 patients reported upon were alive at the time of this review, 37 were dead and 36 had been lost to follow-up.     

Parkinson Subtypes Progress Differently in Clinical Course and Imaging Pattern

Objective

To elucidate whether Parkinson’s disease (PD) subtypes show a differential pattern of FP-CIT-SPECT binding during the disease course.

Methods

We examined 27 patients (10 female, 17 male, mean age 61.68±11.24 years, 14 tremordominant, 13 akinetic-rigid) with [¹²³I]FP-CIT-SPECT and clinical ratings including UPDRS III after at baseline and after a mean period of 2.47 years. Patients had been classified at baseline as tremordominant or akinetic-rigid according to a “tremor score” and “non-tremor score”. These subgroups were compared for differences in disease progression. Means of clinical ratings and the quantitative analyses of FP-CIT-SPECT for ipsi- and contralateral putamen and caudate nucleus were calculated and compared between baseline and follow-up.

Results

There were no statistical differences concerning age, disease duration, L-Dopa equivalent dose, disease severity (UPDRS III) or dopaminergic uptake in FP-CIT-SPECT at baseline between both subgroups. At follow-up, akinetic-rigid patients showed a distinct and statistically significant reduction of the dopaminergic uptake associated with significant progression of the clinical symptoms (UPDRS III). In contrast, in tremor patients the aggravation of clinical symptoms and dopaminergic deficit was less pronounced without statistical significance among assessments.

Conclusions

This study shows for the first time a considerable progression of clinical symptoms and in-vivo dopaminergic deficit of akinetic-rigid compared to tremordominant PD patients over time. Our data may help to improve strategic planning of further therapeutic trials and to provide a clearer prognosis for patients regarding the perspective of their disease.     

Disturbances of Pulmonary Function in Mitral Valve Disease

To study the sequence of changes in respiratory function that occur in the natural history of mitral stenosis, and the physiological basis of “cardiac dyspnea”, 30 patients with chronic mitral valve disease were subjected to detailed pulmonary function tests. There was no significant change in vital capacity and functional residual capacity. The reduction in maximal mid-expiratory flow rate showed excellent correlation with the respiratory symptoms. The pulmonary capillary blood volume was increased in moderately advanced cases but was consistently reduced in the severest cases. Hyperventilation was due to an increased respiratory rate. Dyspnea was associated with increased respiratory work owing to the interrelation between the reduction in diffusion capacity, compliance, cardiac output, the increase in airway resistance, and the uneven ventilation and perfusion of the lungs. The amount of “effort” required to breathe is incommensurate with the external load in these patients.     

Fabry Disease – Underestimated in the Differential Diagnosis of Multiple Sclerosis?

Objective

Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.

Methods

Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.

Results

Four patients were identified as having a “possible” history of MS, and 7 patients as “definite” cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.

Conclusion

There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.     

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.     

NON-TOXIC GOITER TREATMENT WITH I-TRIIODOTHYRONINE AND I-THYROXINE

Twenty-one patients with goiters—four diffuse and 17 nodular—were treated with I-triiodothyronine and I-thyroxine in doses to tolerance. The four diffuse goiters were barely palpable at the end of the treatment. The average dose of I-triiodothyronine required was 100 mcg. per day. The average dose of I-thyroxine was 0.3 mg. per day. Of the 17 multinodular goiters, 11 showed at least a 50 per cent reduction in size. The average dose of I-triiodothyronine used was 125 mcg. In six cases the gland did not change in size; in three of the six the lesion was diagnosed, at operation, as microfollicular and macrofollicular colloid goiter.Hypermetabolic symptoms may occur when doses of 100 mcg. or more of I-triiodothyronine are used.Results indicated that suppressive therapy with thyroid hormone to tolerance is effective in diffuse goiters. It is only partially effective in the treatment of multinodular goiters. In the cases in which operation was done, no change in the basic histological goiter structure was observed.     

Tuberculosis: A Challenge to the General Practitioner

Of 157 patients dying of tuberculosis in Ontario (1960) 132 (87.4%) suffered from the pulmonary form of the disease (incidence 2.6 per 100,000). In the same year, 1632 of 1847, or 88.3%, active new cases reported had the pulmonary type and 183 additional cases were reported without details as to type of disease. Thus, in 1960, a total of 2030 new cases of tuberculosis were reported in Ontario.Of 1367 patients with pulmonary tuberculosis (reinfection type), 357 (26.1%) had “far advanced” disease and 613 (44.8%) had “moderately advanced” disease.This high percentage of patients with “moderately advanced” to “far advanced” disease at the time of diagnosis constitutes the real challenge to physicians in private practice, who made the diagnosis in 45% of cases.Emergence of resistant strains of bacteria increases the urgency of prompt diagnosis and treatment. The most vulnerable population segment is the 15-30 year age-group, many of whom are negative intracutaneous reactors. A high index of suspicion is necessary, particularly in certain segments of the population with a high incidence of infection, combined with a careful history, meticulous physical examination, intracutaneous tests, chest and other radiographs, and appropriate bacteriological studies.     

Cytokine Response Signatures in Disease Progression and Development of Severe Clinical Outcomes for Leptospirosis

Background

The role of the immune response in influencing leptospirosis clinical outcomes is not yet well understood. We hypothesized that acute-phase serum cytokine responses may play a role in disease progression, risk for death, and severe pulmonary hemorrhage syndrome (SPHS).

Methodology/Principal Findings

We performed a case-control study design to compare cytokine profiles in patients with mild and severe forms of leptospirosis. Among patients hospitalized with severe disease, we compared those with fatal and nonfatal outcomes. During active outpatient and hospital-based surveillance we prospectively enrolled 172 patients, 23 with mild disease (outpatient) and 149 with severe leptospirosis (hospitalized). Circulating concentrations of pro- and anti-inflammatory cytokines at the time of patient presentation were measured using a multiplex bead array assay. Concentrations of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, and TNF-α were significantly higher (P<0.05) in severe disease compared to mild disease. Among severe patients, levels of IL-6 (P<0.001), IL-8 (P = 0.0049) and IL-10 (P<0.001), were higher in fatal compared to non-fatal cases. High levels of IL-6 and IL-10 were independently associated (P<0.05) with case fatality after adjustment for age and days of symptoms. IL-6 levels were higher (P = 0.0519) among fatal cases who developed SPHS than among who did not.

Conclusion/Significance

This study shows that severe cases of leptospirosis are differentiated from mild disease by a “cytokine storm” process, and that IL-6 and IL-10 may play an immunopathogenic role in the development of life-threatening outcomes in human leptospirosis.     

CHOLANGIOGRAPHY FOLLOWING COMMON DUCT DRAINAGE

In a series of 197 patients with extrahepatic biliary disease, 65 who had symptoms that met certain established criteria were operated upon to explore the common bile duct for stones. Stones or debris were found in 34 cases.Certain phases of the procedure used are being reevaluated.Because of unsatisfactory results with immediate cholangiograms, they were made only in selected cases in which the anticipated advantages outweighed the known disadvantages. Delayed cholangiography (10 or 12 days postoperatively) is considered a “must,” however, for determination of the presence of remaining stones. If residual stones are shown, they are removed as soon as possible.     

Fingerprint Patterns in Huntington's Chorea and Parkinson's Disease

In the course of a continuing search for means of predicting Huntington''s chorea before the onset of neurological symptoms, a study of fingerprint patterns was undertaken, using the technique employed by Hodges and Simon in the investigation of patients with Wilson''s disease. Fingerprint patterns of 61 patients with Huntington''s chorea and 50 with Parkinson''s disease were compared with norms established by Scotland Yard. Although an increased incidence of the “whorl” pattern was seen in the left second and third fingers in patients with Huntington''s chorea, this finding could not be interpreted as having diagnostic or prognostic value as it was found also in some normal subjects and in occasional cases of Parkinson''s disease. The pattern supposedly characteristic of Wilson''s disease was also seen in persons with Huntington''s chorea.     

Non-Tuberculous Chest Disease Found in a Mass X-Ray Survey in Vancouver,B.C

In 1964, 219,085 persons were examined during a tuberculosis survey in Vancouver, B.C. One hundred and fifteen new cases of tuberculosis and 929 cases of significant non-tuberculous lung disease were found. In a four-month follow-up of the non-tuberculous cases it was found that of the 742 patients who had named a physician when examined 26.6% had not made contact with him. Of those who did contact the physician, the follow-up was considered “poor” in only 30 patients (2.1%). Seventeen patients had died in the four-month interval and 81 who could not be located after the initial survey were considered “lost”. Rates were determined for 37 diagnoses per 1000 patients screened. The most common diagnosis was localized pulmonary fibrosis (1.69/1000). Carcinoma was found in 0.30/1000 and solitary lung density in 0.17/1000 population screened.     

Membranoproliferative Glomerulonephritis and Persistent Hypocomplementaemia

The clinical, laboratory, and histological findings of 50 patients with membranoproliferative glomerulonephritis are described. Three-quarters of the patients, who were mostly older children and young adults, presented clinically with a mixture of “nephritic” and “nephrotic” symptoms; the remaining quarter had no symptoms and were diagnosed after the discovery of proteinuria and microscopic haematuria.Though this clinical picture may occur in other forms of glomerulonephritis, the patients described here were unified as a group by their glomerular morphological appearance—namely, a combination of mesangial proliferation and capillary wall thickening, mainly due to subendothelial accumulations of mesangial matrix.In 68% serum C3 (β10-globulin) levels were reduced initially, while a further 16% subsequently showed a fall to abnormally low levels. All patients had substantial proteinuria, usually of moderately impaired selectivity, and all but one had haematuria in addition. Children frequently presented with an illness resembling acute nephritis, whereas adults usually had a nephrotic syndrome from the start.In 31 patients, followed for periods of one to eight and a half years, serial measurements of glomerular filtration rate were made. Sixteen have experienced no deterioration of renal function, though their proteinuria continues unchanged. Fifteen have shown progressive deterioration; six of them are still well, six are on regular dialysis treatment, and three have died. Treatment with corticosteroids, azathioprine, or cyclophosphamide, alone or in combination, did not seem to influence the course of the disease, and another two patients died from complications of steroid therapy. The disease usually runs a chronic course and appears to be progressive.     

Unusually High Incidence of Paediatric Coeliac Disease in Sweden during the Period 1973 – 2013

Objective

The prevalence of coeliac disease in Sweden during the “epidemic period” (1984−1996) was one of the highest in the world. The aim of this study was to assess the coeliac disease incidence in our region over the 41-year period, and how diagnostic activity and diagnostic accuracy were affected by the introduction of antibody testing. We also looked into how patients with mild enteropathy were evaluated.

Methods

In the county of Östergötland in Sweden, 2790 paediatric patients were investigated for suspected coeliac disease between 1973 and 2013. Notes were scrutinised for data on sex, age, histopathological reports and final diagnosis. For comparative purposes this period was divided into three sub-periods (1973−1983, 1984−1996 and 1997−2013) named pre-epidemic, epidemic and post-epidemic.

Results

Coeliac disease diagnosis was received by 1,030 patients. The peak incidence rate, 301 cases/100,000 in 1994 for the age group 0−1.9 years is the highest figure ever reported. The other age groups, 2−4.9, 5−14.9, and 15−17.9 years, also had high incidence rates. After the 1984−1996 “epidemic period” the incidence decreased for the youngest group but continued to increase for the other groups. The cumulative incidence at 18 years-of-age for children born during the epidemic reached 14 cases/1000 births, the highest figure hitherto reported. Diagnostic activity differed significantly between the three sub-periods (p<0.001) increasing gradually from 1984 and reaching a peak value of 0.87 in 2012. Cases of mild enteropathy were more frequently regarded as non-coeliac disease cases, decreasing significantly in the “post-epidemic” period (p<0.001).

Conclusions

The incidence rate and cumulative incidence of coeliac disease were possibly the highest ever reported. Changes in diagnostic activity and accuracy could not be attributed to the introduction of new antibody tests, possibly because of other changes e.g. variations in the symptoms at presentation and improved knowledge of the disease among parents and health professionals.     

Leprosy in a prison population: A new active search strategy and a prospective clinical analysis

BackgroundThis study evaluates an active search strategy for leprosy diagnosis based on responses to a Leprosy Suspicion Questionnaire (LSQ), and analyzing the clinical, immunoepidemiological and follow-up aspects for individuals living in a prison population.MethodsA cross-sectional study based on a questionnaire posing 14 questions about leprosy symptoms and signs that was distributed to 1,400 prisoners. This was followed by dermatoneurological examination, anti-PGL-I serology and RLEP-PCR. Those without leprosy were placed in the Non-leprosy Group (NLG, n = 1,216) and those diagnosed with clinical symptoms of leprosy were placed in the Leprosy Group (LG, n = 34).FindingsIn total, 896 LSQ were returned (64%), and 187 (20.9%) of the responses were deemed as positive for signs/symptoms, answering 2.7 questions on average. Clinically, 1,250 (89.3%) of the prisoners were evaluated resulting in the diagnosis of 34 new cases (LG), based on well-accepted clinical signs and symptoms, a new case detection rate of 2.7% within this population, while the NLG were comprised of 1,216 individuals. The confinement time medians were 39 months in the LG while it was 36 months in the NLG (p>0.05). The 31 leprosy cases who responded to the questionnaire (LSQ+) had an average of 1.5 responses. The symptoms “anesthetized skin area” and “pain in nerves” were most commonly mentioned in the LG while “tingling, numbness in the hands/feet”, “sensation of pricks and needles”, “pain in nerves” and “spots on the skin” responses were found in more than 30% of questionnaires in the NLG. Clinically, 88.2% had dysesthetic macular skin lesions and 97.1% presented some peripheral nerve impairment, 71.9% with some degree of disability. All cases were multibacillary, confirming a late diagnosis. Anti-PGL-I results in the LG were higher than in the NLG (p<0.0001), while the RLEP-PCR was positive in 11.8% of the patients.InterpretationOur findings within the penitentiary demonstrated a hidden prevalence of leprosy, although the individuals diagnosed were likely infected while living in their former communities and not as a result of exposure in the prison. The LSQ proved to be an important screening tool to help identify leprosy cases in prisons.     

THE USE OF BANTHINE IN THE TREATMENT OF DIGESTIVE DISTURBANCES

Banthine® was used in the treatment of patients with various diseases, organic and functional, of the gastrointestinal tract. Good response was obtained in a high proportion of cases of duodenal, stomal and gastric ulcer, and of hypertrophic gastritis. In some instances, patients who did not have good response at first were relieved later when the size of doses and the dosage schedule were adjusted to fit their particular needs.Some patients “felt so well” during Banthine therapy that they departed from prescribed diet and violated injunctions against use of alcohol and tobacco, and symptoms recurred.Nine patients with history of recurrent bouts of pain from ulcer for several years took small doses of Banthine constantly, or occasionally at times of stress, as a prophylactic measure after the symptoms were relieved by therapeutic doses. None of them had recurrence while following the prophylactic regimen.In most of the cases of peptic ulcer in which the response was recorded as “poor,” it was because distressing side-effects dictated discontinuance of the drug. Several elderly male patients had severe urinary retention. Paralytic ileus developed postoperatively in one patient who was receiving Banthine. Less severe side reactions—dry mouth, blurring of vision, urinary slowing — were for the most part transient.Few patients with functional indigestion, chronic non-specific colitis or regional enteritis were relieved. Most of the patients with functional indigestion reported exacerbation of symptoms when Banthine was given. This was believed to be based on emotional reaction to the hypomotility induced by the drug.