Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism

Alterations in muscle structure and function have been reported in overt hypothyroidism, with decreased activity of enzymes involved in anaerobic and oxidative glucose metabolism. To test whether similar changes in muscle energy metabolism are present in subclinical hypothyroidism (sHT), we studied 12 patients with sHT who complained of mild neuromuscular symptoms. The control group included 10 sex- and age-matched healthy volunteers. Skeletal muscle lactate and pyruvate production were determined in the resting state and during dynamic arm exercise. During exercise, blood lactate was significantly higher in sHT patients than in controls from the third exercise step onward (P = 0.02 at 30%, p = 0.008 at 40%, and P = 0.002 at 50% of maximal voluntary contraction). Moreover, the mean increment in blood lactate during exercise was positively related (r2 = 0.44; P = 0.02) to the duration of sHT, but not to serum levels of TSH, free T3, or free T4. No significant difference was found in blood pyruvate concentrations between the two groups at baseline or during exercise. Thus, the lactate/pyruvate ratio curve paralleled the lactate curve in patients as well as controls. We conclude that muscle energy metabolism is impaired in sHT in rough proportion to the known duration of the disease. Early L-T4 therapy may be useful not only to provide specific treatment for such metabolic changes, but also to avoid progression to frank hypothyroidism.     

Clinical and biochemical phenotype in 11 patients with mevalonic aciduria

OBJECTIVE: Mevalonic aciduria is a consequence of the deficiency of mevalonate kinase, the first enzyme after 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the biosynthesis of cholesterol and nonsterol isoprenes. To establish the clinical and biochemical phenotype of mevalonic aciduria, the authors assembled their experience with 11 patients including attempts at therapeutic interventions. METHODS: Mevalonic acid in body fluids was determined by stable isotope dilution gas chromatography/mass spectroscopy with selected ion monitoring, ubiquinone-10 concentrations by reversed-phase high-pressure liquid chromatography. RESULTS: Varying degrees of severity of clinical illness were observed despite uniform, virtual absence of residual activity of the enzyme. The most severely affected patients have had profound developmental delay, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, and anemia, as well as diarrhea and malabsorption, and have died in infancy. Less severely affected patients have had psychomotor retardation, hypotonia, myopathy, and ataxia. All patients have had recurrent crises in which there was fever, lymphadenopathy, increase in size of liver and spleen, arthralgia, edema, and a morbilliform rash. Neuroimaging studies revealed selective and progressive atrophy of the cerebellum. Mevalonic acid concentrations were found to be grossly elevated in body fluids of all patients. Concentrations of plasma cholesterol were normal or only slightly reduced. Concentrations of ubiquinone-10 in plasma were found to be decreased in most patients. Abnormalities such as hypoglycemia, metabolic acidosis, or lactic acidemia, the usual concomitants of disorders of organic acid metabolism, were conspicuously absent. CONCLUSIONS: These observations establish the broad range of clinical symptoms and biochemical findings in mevalonic aciduria. It is concluded that although patients with mevalonic aciduria have a recognizable phenotype of serious clinical manifestations, some patients are likely to remain undiagnosed and may be found in a variety of subspecialty clinics, including neurology, gastroenterology, cardiology, and genetics.     

Colorectal cancer. Clinical and pathologic features

Despite an improved understanding of the pathogenesis of colorectal cancer and the technical ability to alter its natural history in a large proportion of average and high-risk patients, this cancer remains deadly. There has been no significant change in incidence or survival rates over the past 40 years. This indicates a continued need for earlier detection of polyps and cancers, aggressive surgery for the primary tumor, and improved multimodality treatment for metastatic disease.     

Clinical and microscopical features of small-intestinal microsporidiosis in patients with AIDS

Intestinal microsporidiosis by Enterocytozoon bieneusi is an increasingly recognized infection in AIDS patients. We report eight cases of microsporidiosis. All patients were severely immunodepressed. Clinical features were highly variable. Patients were followed up for a mean period of 7.8 months. All patients had persistent infection during the follow-up and spore excretion remained constant. Two patients became asymptomatic during the follow-up. None of the patients presented clinical and echographic signs of biliary involvement. Treatment with albendazole, metronidazole or paromomycin failed to produce a durable clinical response or to eradicate the organism. Cases were identified by stool examination and additionally investigated with light and electron microscopy. It was found that light microscopy was a sensitive method, while electron microscopy was less sensitive but allowed the definition of the infecting species. The modified trichrome stain was a satisfactory method for diagnosis on fecal smears. The calcofluor stain and the combination of DAPI with calcofluor was a rapid and simple staining method for screening.     

Primary cysts of the iris pigment epithelium. Clinical features and natural course in 234 patients

OBJECTIVE: To describe the clinical characteristics, natural course, and complications of a large group of patients with primary iris pigment epithelium (IPE) cysts. DESIGN: Observational case series. PARTICIPANTS: Two hundred thirty-four patients with primary IPE cysts participated. RESULTS: Primary IPE cysts were classified as central in 6 patients (3%), midzonal in 50 patients (21%), peripheral in 170 patients (73%), and dislodged in 8 patients (3%). Central (pupillary) IPE cysts were found only in males, peripheral IPE cysts were found most often in females (69%), and no gender predilection was detected for midzonal and dislodged IPE cysts. Central and peripheral IPE cysts occurred in young patients (mean age, 20 and 33 years, respectively), whereas midzonal and dislodged IPE cysts were seen in slightly older patients (mean age, 52 and 45 years, respectively). Central IPE cysts were visible when the pupil was not dilated and appeared most often as a round or collapsed brown lesion arising from the pupillary margin, most commonly superonasally. Midzonal IPE cysts were brown and fusiform, best visualized after pupillary dilation. Peripheral IPE cysts produced a characteristic bulging in the iris stroma near the iris root, but they were directly visible in only 78% of cases. After wide dilation and patient and slit-lamp positioning, they appeared as a round clear lesion behind the iris, most often in the inferotemporal quadrant. Finally, dislodged IPE cysts appeared as a brown oval lesion, free floating in the anterior chamber (12%) or in the vitreous (12%), or fixed in the anterior chamber angle (75%). One hundred twenty-four patients (53%) were followed for a mean of 35 months (range, 3 months-19 years). In these patients, complications associated with IPE cysts included lens subluxation in one case (1%), iritis in one case (1%), focal cataract in two cases (2%), glaucoma in two cases (2%), and corneal touch in five cases (4%). CONCLUSION: Primary IPE cysts have characteristic clinical features that serve to differentiate them from intraocular malignancies. Most cysts have a benign clinical course, and treatment is rarely necessary.     

Clinical features and outcome in disseminated mycobacterial diseases in AIDS patients in Taiwan

OBJECTIVE: To describe and compare the clinical features and outcome of disseminated tuberculosis (TB) and Mycobacterium avium complex (MAC) disease in AIDS patients. DESIGN: Prospective cohort study. SETTING: A 1800-bed university teaching hospital, the largest centre for HIV/AIDS patients in Taiwan. METHODS: From July 1994 through June 1997, a standardized protocol was used to record the demographic and clinical features in all hospitalized HIV-infected patients, and to perform routine studies and invasive procedures for diagnosis of disseminated mycobacterial diseases. To compare the survival, control patients were selected from the HIV-infected patients hospitalized in the same hospital during the same study period, and had similar age, sex, CD4+ cell counts and antiretroviral therapy regimens. RESULTS: A total of 22 cases of disseminated TB and 15 cases of disseminated MAC were identified. Disseminated TB and MAC occurred in patients with similarly low CD4+ cell counts (median, 23 versus 5 x 10(6)/l; P = 0.08). The clinical features favouring disseminated TB included night sweats, peripheral lymphadenopathy, acid-fast bacilli in sputum smears, chest radiographic findings of hilar enlargement, and lack of prior AIDS-defining illnesses. Hepatosplenomegaly, elevated serum alkaline phosphatase (more than twice the upper limit of normal), elevated serum gamma-glutamyl transpeptidase (more than three times the upper limit of normal), and leukopenia favoured disseminated MAC. The patients with disseminated TB survived much longer than patients with disseminated MAC (mean survival, 96 versus 22 weeks, P = 0.008) but had a similar outcome to control patients (P = 0.60). CONCLUSION: Disseminated TB and MAC are distinguishable by clinical features in AIDS patients with similar immunocompromised states. Those features may facilitate diagnosis and selection of specific therapeutic regimens. Disseminated TB was not associated with a shortened survival period in AIDS patients when they completed anti-TB treatment. In contrast, disseminated DMAC was associated with shortened survival despite treatment with potent regimens. These results may emphasize the importance of prophylaxis for MAC in this population.     

Moyamoya and Down syndrome. Clinical and radiological features

BACKGROUND AND PURPOSE: Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by progressive stenosis of the supraclinoid internal carotid artery, with the secondary development of enlarged basal collateral vessels. It may occur as a primary disease or as a syndrome in association with a variety of conditions, and its pathogenesis remains unexplained. There are relatively few reports describing the occurrence of moyamoya in Down syndrome. The aim of this study is to describe the clinical and radiological features of moyamoya syndrome associated with Down syndrome (MM-DS) and to explore theories of moyamoya pathogenesis in these patients. METHODS: Seven children with MM-DS underwent brain imaging, transfemoral angiography, and serial neurological exams. Neurological deficits, poststroke recovery, radiographic infarct characteristics, and angiographic abnormalities were reviewed. RESULTS: The clinical and radiological features of primary moyamoya disease overlap with those of MM-DS. Hemiplegia and aphasia were the most common presentations. Motor recovery was excellent in five of seven cases. Cerebral infarcts were superficial or deep and can occur in a watershed distribution. Angiography demonstrated involvement of the internal carotid artery and its branches bilaterally in all seven cases and the posterior cerebral arteries in four cases. CONCLUSIONS: The clinical and radiological features of MM-DS overlap with primary moyamoya disease. We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of moyamoya disease. Although the neuronal substrate is abnormal in Down syndrome patients, recovery from hemiplegic stroke in patients with MM-DS is comparable to recovery in patients with primary moyamoya.     

Hartnup disease. Clinical, pathological, and biochemical observations

Hartnup disease is a rare genetic disorder of amino acid transport associated with variable and intermittent clinical abnormalities. A family is described in which three siblings had an intermittently progressive neurological disease and two of the affected siblings had the Hartnup-pattern aminoaciduria. Neuropathological examination of one case showed severe diffuse atrophy, generalized neuronal loss in the cortex, and Purkinje cell loss in the cerebellum. In vivo and in vitro studies of intestinal amino acid transport in the surviving sibling indicated a partial defect in the transport of several neutral amino acids (tryptophan, alanine, serine, and methionine) with normal transport of other neutral amino acids (threonine, phenylalanine, histidine, tyrosine, and isoleucine). Transport of glycine, proline, hydroxyproline, and the basic amino acids appeared normal.     

Clinical and laboratory features of 100 patients with perennial allergic rhinitis

100 patient records were studied with a clinical diagnosis of perennial allergic rhinitis; they were 66 women and 34 men, with a range of 28.6 years old. The cutaneous tests were positive to pollens in 78% of the cases, fungus 39%, inhalables 39%, Dermatophagoides 19% and bacterial 7%. In the nasal mucous culture the following germs were isolated: S epidermidis 49%, S aureus 25%, Neisseria sp 15%, Corynebacterium 2%, P mirabilis 1% and E coli 1%. The nasal cytology was positive in 25% of the cases for the presence of eosinophils, and was negative in 75%. In only 27% of the patients eosinophil was found in the peripheric blood. The results are commented and the utility of the cultivation of nasal mucous and of the cytology of nasal mucous in patients with perennial allergic rhinitis is discussed.     

Seizure disorders in the dog. 1. Clinical features and differential diagnosis

For differential diagnosis, therapy, and prognosis of seizures in dogs it is recommended to distinguish between two groups of diseases: 1. Epilepsy is diagnosed if seizures occur repeatedly without an active, underlying disorder. Idiopathic epilepsy occurs most commonly. A hereditary component has been demonstrated in several breeds. Symptomatic epilepsy results from previous resolved forebrain disorders, which cause epileptic seizures through scar formation. 2. Seizures are caused by active structural forebrain disease or metabolic-toxic imbalances. Upon initial presentation of the dog, a preliminary classification may be achieved with the seizure history, clinical and neurological examination, and routine laboratory evaluation. The diagnosis of idiopathic epilepsy is based on typical seizure history and exclusion of structural forebrain disease and metabolic-toxic imbalances with special laboratory testing, CSF examination, and brain scanning procedures.     

Leigh syndrome: clinical features and biochemical and DNA abnormalities

The morphology and number of cells in the trophectoderm (TE) and inner cell mass (ICM) of buffalo blastocysts derived from in vitro fertilization and cultured in the presence or absence of insulin-like growth factor-I (IGF-I) were analyzed by differential fluorochrome staining technique. The total cell number (TCN), TE number, and ICM cell number were significantly higher in blastocysts developed in vitro in the presence of IGF-I as compared to blastocysts developed without IGF-I (P < 0.01). It was observed that the buffalo blastocyst took 5-9 days postfertilization to develop in vitro. In order to correlate the time required for blastocyst development and the allocation of cells to TE and ICM, blastocysts were designated as fast (developing on or before day 7) or slow (developing after day 7). The TCN, TE, and ICM cells of fast-developing blastocysts cultured in the presence of IGF-I were significantly higher than slow-developing blastocysts (P < 0.01). The blastocysts developed on day 6 had a mean total cell number 118.6 +/- 21.4, which significantly decreased to 85.6 +/- 17.4, 62.0 +/- 14.5, and 17.0 +/- 4.0 on days 7, 8, and 9, respectively (P < 0.05). Normal development of buffalo embryo showed that, on average, embryos reached compact morula stage at the earliest between days 4.5-5.5. Blastocysts developed, at the earliest, between days 5.0-6.0, and it took them, on average, 6.5 days to hatch from the zona pellucida. TCN, TE, and ICM increased three times from morula to blastocyst; however, the proportion of ICM to TCN remained the same, in both embryonic stages. TE approximately doubled in hatched blastocysts, as compared to unhatched blastocysts (P < 0.05). However, ICM cells were decreased. The time required for development of parthenogenetic blastocysts was observed to be greater as compared to in vitro fertilized (IVF) blastocysts. The total cell number of parthenogenetic blastocysts was 100.8 +/- 11.3, including 59.2 +/- 8.4 cells of TE and 42.1 +/- 6.9 cells of ICM.     

Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism

Obstetrics is one of the most demanding yet rewarding disciplines required of rural general practice although rising medical indemnity fees combined with medico-legal interest in this discipline make the current rural generalist obstetricians a threatened species. These factors, plus the difficulty generalist registrars have in obtaining good procedural training in this specialist field make obstetric practice less than attractive for future rural general practitioners. This article provides a brief overview of rural obstetric practice from the perspective of a rural generalist obstetrician with 18 years experience. Case studies are used to highlight the challenges of this field.     

Inflammatory bowel disease: Part I. Clinical features and diagnosis

Familial and epidemiologic studies of inflammatory bowel disease indicate a strong genetic predisposition that is modified by certain environmental factors. Abnormal submucosal immune activation may be important in the etiology of the disease. Yersinia enterocolitica infection, various "gay bowel syndromes" and other recently described enteric infections often mimic Crohn's disease. An initial barium study is useful in documenting the extent of disease and complications. Endoscopic biopsy confirms the surface appearance and histologic features of inflammatory bowel disease. Newer photodocumentation techniques are expected to improve the comparability of endoscopic observations. Complications of inflammatory bowel disease occur frequently, may involve any organ system and may precede the onset of bowel symptoms.     

Clinical features of halothane and enflurane

This is a brief review of some of the salient clinical features of halothane and enflurane, the two most widely used volatile anesthetics in clinical practice today. Although, halothane has an excellent safety record and comes close to being the ideal inhalational anesthetic it does have some undesirable effects, including incompatibility with adrenaline and the possibility of causing disturbed hepatic function when given repeatedly. Enflurane is now established as a satisfactory volatile anesthetic which has considerably less metabolic breakdown than many other agents; if this is reflected in terms of minimal organ toxicity it should continue to have considerable clinical value. The risks of damage to the kidney and cerebral irritability are uncommon but undesirable features of enflurane. In the search of the perfect inhalational anesthetic the most promising compounds will be those with least biotransformation, suitable pharmacokinetics with minimal cardiovascular or respiratory depression and without toxic effects on the liver, kidney or foetus.