The 'worn-out athlete': a clinical approach to chronic fatigue in athletes.

Chronic fatigue in the athletic population is a common but difficult diagnostic challenge for the sports physician. While a degree of fatigue may be normal for any athlete during periods of high-volume training, the clinician must be able to differentiate between this physiological fatigue and more prolonged, severe fatigue which may be due to a pathological condition. As chronic fatigue can be the presenting symptom of many curable and harmful diseases, medical conditions which cause chronic fatigue have to be excluded. The clinician must then be able to differentiate between chronic fatigue associated with training or chronic fatigue from other medical causes, and also between the chronic fatigue syndrome and the overtraining syndrome. Once the clinician has excluded all of the above medical conditions which cause chronic fatigue in athletes, a significant proportion of fatigued athletes remain without a diagnosis. Novel data indicate that skeletal muscle disorders may play a role in the development of symptoms experienced by the athlete with chronic fatigue. The histological findings from muscle biopsies of athletes suffering from the 'fatigued athlete myopathic syndrome' are presented. We have designed a clinical approach to the diagnosis and work-up of the athlete presenting with chronic fatigue. The strength of this approach is that it hinges on the participation of a multidisciplinary team in the diagnosis and management of the athlete with chronic fatigue. The athlete, coach, dietician, exercise physiologist and sport psychologist all play an important role in enabling the physician to make the correct diagnosis.

Characterisation of a lipoprotein in Mycobacterium bovis (BCG) with sequence similarity to the secreted protein MPB70.

The monoclonal antibody, mAb3C4, raised against sonicated Mycobacterium bovis (Mb) BCG (Tokyo strain 172) cells recognises a 23-kDa protein in the cell wall. The gene encoding this protein was cloned and sequenced and found to be 100% homologous to mpb83 and mpt83 and the putative protein to have a 76% sequence similarity to the secreted, Mb-specific protein, MPB70. MPB83 contains the amino acid (aa) sequence LAGC, which corresponds to the consensus sequence for bacterial lipoprotein modification and processing. MPB83 associated with the detergent phase when separated with Triton X-114 confirming that it is a lipoprotein. When the putative site of acylation, the Cys in the sequence LAGC, was substituted with Ser, the mutated MPB83 associated with the aqueous phase. The cloned gene was used to determine the distribution of mpb83 in various Mycobacterium species. The gene was present in the M. tuberculosis (Mt) complex organisms, as well as in M. kansasii. In addition, Southern blot analysis of Mb and Mt DNA indicated that the mpb83 and mpb70 genes are located close to each other on the genome. Western blot analysis of cell lysates of various Mycobacterium species indicated that only Mt H37Rv and H37Ra produced proteins which reacted with mAb3C4. Furthermore, only two out of six of the Mb field isolates produced detectable antigen, indicating that expression of the mpb83 gene is variable within the Mt complex organisms.

Paediatric rhabdomyosarcoma: MyoD1 demonstration in routinely processed tissue sections using wet heat pretreatment (pressure cooking) for antigen retrieval.

AIMS: To investigate wet heat pretreatment (pressure cooking) as a means of antigen retrieval for demonstration of MyoD1 in paraffin wax embedded tissue. METHODS: Routinely processed tissue sections of transmission electron microscope confirmed cases of rhabdomyosarcoma were stained immunohistochemically with the MyoD1 antibody. Antigen retrieval was achieved by wet heat pretreatment of the tissue sections. RESULTS: MyoD1 was stained successfully in all seven cases. The protein was localised to nuclei and cytoplasm depending on the type of tumour cell. CONCLUSIONS: Wet heat pretreatment for antigen retrieval from routinely processed tissue sections permits excellent subsequent immunostaining for MyoD1 in rhabdomyoblasts.

Pearson's syndrome presenting with Fanconi syndrome.

A case of Pearson's marrow-pancreas syndrome is presented. The dominant clinical feature was a generalized disorder of proximal tubule function with severe renal magnesium wasting. Renal and muscle biopsies were performed and showed bizarre giant mitochondria.

Pluripotential melanoblastoma, a unifying concept on malignancies arising in congenital melanocytic nevi: report of two cases.

Congenital melanocytic nevi are benign lesions present at birth and considered to be caused by a maldevelopment of the neural crest. The malignant potential of the congenital melanocytic nevi have been extensively addressed by several authors, and malignant melanoma is the most frequent neoplasm arising in these lesions. The present report describes two patients with congenital melanocytic nevi in which malignant melanoma with undifferentiated areas showing rhabdomyoblastic differentiation developed. The findings suggest that these mixed neoplasms may be recapitulating the differentiation potential of the ectomesenchyme-neural crest cells. We advocate the term "melanoblastoma" when referring to them.

Malignant ectomesenchymoma in childhood.

Five childhood malignant ectomesenchymomas are reported from three centers in three countries. The children were all younger than 3 years (four less than 12 months), four were boys, and four tumors were sited in the pelvis or external genitalia. All tumors had distinctive light microscopic features of rhabdomyosarcoma and three also demonstrated small numbers of included neuronal cells. Immunohistochemical studies and transmission electron microscopy revealed the additional presence of neurogenic components in the remaining two patients. An additional epithelial component was found by immunohistochemistry in one tumor, which suggests a pluripotential origin that still requires karyotypic investigation. Aggressive chemotherapy and adequate surgical excision have thus far been effective in providing disease-free follow-up for periods of 7 to 50 months. It is implied that because the biological behavior and morphology closely resemble those of rhabdomyosarcoma and because the neurogenic component is often inconspicuous, many malignant ectomesenchymomas may be misdiagnosed as rhabdomyosarcomas.

Effect of lidocaine on in vivo hepatic function.

Lidocaine is administered to assess donor or recipient liver function during hepatic transplantation. This study was performed to determine whether lidocaine administered at a constant concentration affected hepatic function or had demonstrable effects on hepatocellular ultrastructure. Fourteen pigs were randomly allocated to receive either a two-stage infusion of lidocaine hydrochloride or of saline. Transhepatic blood samples were taken and ultrasonic portal venous and hepatic arterial blood flow readings made on animals anesthetized with isoflurane in nitrous oxide. Liver biopsies were taken for histological analysis and determination of adenine nucleotide status prior to and after 2 hr of the two-stage infusion. A mean systemic constant plasma lidocaine concentration of 5.9 micrograms/ml was achieved during the second hour of infusion. There were no differences between the two groups in a large number of indices of hepatic function and plasma composition prior to and during the second hour of the respective infusions. Hepatic blood flow was also similar at these times. On histological examination there were no electron microscopic changes that could be specifically attributed to the administration of lidocaine. However, there were progressive changes with time. This study suggests that in anesthetized pigs a constant lidocaine concentration of about 6 micrograms/ml has no detrimental effect on hepatic function. Progressive hepatic ultrastructural changes occurred that could not be attributed to the administration of lidocaine. These may be the result of anesthetic administered or the surgery performed.

Morphologic features of the myopathy associated with chronic renal failure.

Our previous studies indicate that impaired function of skeletal muscle limits the exercise tolerance of patients with end-stage renal failure who are either maintained on dialysis or undergo renal transplantation. To study the morphology of the condition, muscle biopsies were performed on eight patients with renal failure-associated myopathy. Control samples were taken from seven healthy athletes undergoing knee surgery and from five otherwise healthy but untrained subjects. Tissues were examined by routine light and transmission electron microscopy. Histochemical staining of frozen sections for myosin adenosine triphosphatase and quantitative computer-assisted morphometry of the fiber type and size was performed. The mean (+/- SD) size for type I fibers in patients was 61.2 +/- 11.8 microns, while type II fibers measured 46.7 +/- 11.4 microns. The mean percentage of type II fibers was 67% +/- 12%. These values are within the normal population range and were not different from controls. Significant changes were found on light microscopy of patient samples. These included fiber splitting, internalized nuclei, nuclear knots, moth-eaten fibers, fiber degeneration and regeneration, increased content of lipid droplets, and fiber-type grouping. Electron microscopy showed a large variety of nonspecific abnormalities, including mitochondrial changes, Z-band degeneration, myofilament loss, and accumulation of intracellular glycogen. Ten of 12 control subjects showed no such changes; minor abnormalities were noted on both light and electron microscopy in the remaining two subjects. Muscle oxidative capacity (19.5 +/- 5.1 microL O2/min) for patients with end-stage renal failure was not different from values for those who had undergone renal transplantation, but was lower than values found in trained athletes.(ABSTRACT TRUNCATED AT 250 WORDS)

Childhood pulmonary blastoma: a pleuropulmonary variant of the adult-type pulmonary blastoma.

Two fatal childhood cases of the rare pulmonary blastoma are reported. One was associated with a congenital cystic adenomatoid malformation. Both neoplasms extended to involve visceral pleura and were entirely composed of blastemal and mesenchymal elements without recognizable neoplastic epithelial components. The mesenchymal component in both instances consisted of malignant rhabdomyoblasts, undifferentiated mesenchyme, and differentiated, apparently benign, cartilage. Review of the literature suggests that these features may be specific for the childhood forms of pulmonary blastoma. It is further suggested that pulmonary blastoma, malignant mesenchymoma of the lung, and primary pulmonary rhabdomyosarcoma may have a common pathogenetic origin.

A simple technique for preparation of bone marrow or peripheral blood buffy coat cells for electron microscopy.

A simple and rapid method of processing ethylene-diamine-tetra-acetic acid anticoagulated peripheral blood or aspirated bone marrow for electron microscopy is described. The resultant buffy coat pellet is easily processed into epoxy resin. Semithin sections (1 mu) stained with 1% toluidine blue reveal the various stratified cell layers allowing convenient selection for ultramicrotomy and ultrastructural evaluation.

Phakomatous choristoma of the lower eyelid. A light and ultrastructural study.

This article documents the eighth reported case (to our knowledge) of a phakomatous choristoma, a rare congenital tumor of the lower eyelid of infants. Among the eight cases, there was no instance of tumor recurrence recorded nor was there any detectable postoperative eye defect, despite incomplete resection of the tumor in two patients. While usually clinically diagnosed as a dermoid cyst, the highly characteristic histologic features of this entity should allow more frequent recognition. Ultrastructural examination in our case provided additional evidence of its lenticular origin.

Intracisternal paracrystalline serpigenous inclusions: a marker of disordered fibroblastic proliferation.

Three young children with characteristic fibroblastic tumors are presented. These comprised one case each of congenital fibrosarcoma, dermatofibrosarcoma protuberans, and fibrous hamartoma of infancy. Ultrastructural examination in each tumor revealed the presence of a peculiar intracisternal paracrystalline material that exhibited transverse periodicity between 18 and 22 nm. Elongated profiles lying within rough endoplasmic reticulum had a serpigenous outline. It is thought that this material is related to procollagen or its precursors and its presence may signify disorders of fibroblastic proliferation that may occur in fibrous tumors.

Frequent occurrence of microtubuloreticular complexes encountered during routine ultrastructural examination at a children's hospital.

Prompted by our impression that microtubuloreticular complexes (MTRC) are frequently observed during electron microscopy at the Red Cross War Memorial Children's Hospital, Cape Town, we reviewed all specimens submitted for routine ultrastructural examination during a 1-year period. Our impression was confirmed. MTRC were present in a high proportion of cases, especially in vascular endothelium of renal biopsies. As all 9 cases of hepatitis B-associated membranous glomerulonephritis were positive for MTRC, we also reviewed the previous 20 cases with this diagnosis and these were also all positive. Hepatitis B-associated membranous glomerulonephritis is common in our region. MTRC are probably induced by a supposedly uncommon heat labile alpha-interferon. Elevated serum levels of this interferon are known to occur in systemic lupus erythematosus and acquired immunodeficiency syndrome. We propose that children with intercurrent infection in our region frequently respond with alpha-interferon, promoting MTRC formation.

Bilateral renal malakoplakia in infancy.

Two male infants aged 6 months presented with Escherichia coli septicaemia and urinary tract infection. Despite seemingly appropriate antibiotic therapy, a swinging fever, painful enlargement of both kidneys, sterile leukocyturia and renal failure persisted. Excretory urography, ultrasound scan, computerized tomography and magnetic resonance imaging showed diffuse infiltrative disease. 99mTc dimercaptosuccinic acid uptake was minimal, but a 67Ga-citrate scan showed striking diffuse uptake by both kidneys suggestive of inflammatory cell infiltration. Bilateral renal parenchymal malakoplakia was diagnosed on tissue examination. Bilateral parenchymal involvement of the kidneys by this chronic granulomatous disease has not previously been reported in infancy and is fatal if untreated. The lesion is believed infection-induced, due to defective bacterial activity of the macrophages, possibly related to an abnormally low cGMP/cAMP ratio. Treatment with intracellularly active trimethoprim-sulphamethoxazole, rifampicin and ascorbic acid resulted in complete recovery of the one infant so treated over a period of months.

Transient protein losing enteropathy associated with acute gastritis and campylobacter pylori.

Three children presented with acute protein losing enteropathy and were found to have acute gastritis associated with Campylobacter pylori infection. Recovery from protein losing enteropathy was accompanied by resolution of the gastritis and the disappearance of C pylori from the gastric mucosa. Their clinical course suggested that the C pylori had caused the gastritis and the protein losing enteropathy. The association between gastritis caused by C pylori and protein losing enteropathy in children has not to our knowledge been previously described.

Lymphoid tissue of the normal fallopian tube--a form of mucosal-associated lymphoid tissue (MALT)?

Mucosal-associated lymphoid tissue (MALT) is a specialized form of peripheral lymphoid tissue which is found in mucosal surfaces directly or indirectly exposed to the environment. Using immunohistological labeling techniques and electron microscopy, we have explored the possibility that MALT exists in the normal fallopian tube. Immunohistological analysis has demonstrated a striking degree of uniformity in the phenotype of intraepithelial lymphocytes with a predominance of T-lymphocytes of T-cytotoxic/suppressor subtype. Occasional intraepithelial macrophages are also present, but B-cells, T-helper cells, and natural killer cells are absent or are rarely found in the epithelium. Electron microscopy has provided morphological evidence of an interaction between epithelial cells and intraepithelial lymphocytes. The opposing plasma membranes of these two cell types are arranged in the form of complex interdigitations and laminations. These striking arrangements substantially increase the total area of contact between the two cell types. We conclude that MALT does exist in the fallopian tube and that epithelial cells form an integral part of the system. A hypothetical view of the relationship between these cell types is presented.

Endometrial lymphoid tissue: an immunohistological study.

Lymphoid tissue of the endometrium was analysed by histological, immunohistological, and electron microscopical methods in 10 healthy uteri. A panel of monoclonal antibodies recognising macrophages (OKMI), HLA-DR antigen, B lymphocytes, T lymphocytes and their subsets, and dendritic reticulum cells was used in a two stage indirect immunoperoxidase labelling technique. Endometrial lymphoid tissue showed a remarkably consistent pattern of labelling in all cases. Lymphoid tissue was present in three sites: namely, (i) intraepithelial lymphocytes (predominantly T lymphocytes with occasional macrophages) associated with periglandular and sub-epithelial HLA-DR+, OKMI+ macrophages; (ii) interstitial lymphocytes and macrophages; (iii) lymphoid aggregates in the stratum basalis. These were composed mainly of T lymphocytes with a few B lymphocytes. Dendritic reticulum cells were found in those occasional lymphoid aggregates in which germinal centres were present. These features suggest that endometrial lymphoid tissue has many of the hallmarks of mucosal associated lymphoid tissue as found elsewhere in the body--for example, the bronchus and intestine. Endometrial lymphoid tissue appears to be unique, however, in that most of the stratum functionalis in which it is situated shows cyclical shedding during the menstrual cycle.

Papillary and cystic neoplasm of the pancreas--an acinar cell tumour?

Two cases of papillary and cystic neoplasm of the pancreas (PCN) occurring in 17 and 21 year old women are reported with ultrastructural and immunohistochemical findings. A review of the English literature shows that although potentially malignant, PCN, which occurs mainly in young women, is amenable to surgical cure. The significance of large PAS positive and alpha-1-antitrypsin positive tumour granules; the lack of specificity of alpha-1-antitrypsin for pancreatic acinar cells; the possibility of acinar differentiation of PCN; and its separation from pancreaticoblastoma are discussed.