Triple opportunistic pulmonary cavitary disease after cord blood transplantation.

Opportunistic infectious diseases in patients are variable and depend on the host as well as the type of immunosuppression. Cord blood transplant recipients appear to be particularly vulnerable to infectious complications. Sequential or concurrent opportunistic infectious diseases can be particularly difficult to manage and have increased mortality. We present a young patient, status post cord blood transplantation for acute myelogenous leukemia, who developed a large pulmonary mass-like infection with Aspergillus, cytomegalovirus, and Mycobacterium avium complex. Radiological, surgical, and pathological features are described.

Cerebral phaeohyphomycosis caused by Bipolaris spicifera after heart transplantation.

Phaeohyphomycosis is an increasingly recognized cause of brain abscess in both immunocompetent and immunocompromised hosts. We report a case of cerebral phaeohyphomycosis in a 55-year-old male heart transplant recipient caused by Bipolaris spicifera. We review the literature regarding the pathogenesis, epidemiology, diagnosis, and management of infections with dematiaceous fungi.

Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function.

Ultrastructural studies have previously suggested potential association of intermediate filaments (IFs) with mitochondria. Thus, we have investigated mitochondrial distribution and function in muscle lacking the IF protein desmin. Immunostaining of skeletal muscle tissue sections, as well as histochemical staining for the mitochondrial marker enzymes cytochrome C oxidase and succinate dehydrogenase, demonstrate abnormal accumulation of subsarcolemmal clumps of mitochondria in predominantly slow twitch skeletal muscle of desmin-null mice. Ultrastructural observation of desmin-null cardiac muscle demonstrates in addition to clumping, extensive mitochondrial proliferation in a significant fraction of the myocytes, particularly after work overload. These alterations are frequently associated with swelling and degeneration of the mitochondrial matrix. Mitochondrial abnormalities can be detected very early, before other structural defects become obvious. To investigate related changes in mitochondrial function, we have analyzed ADP-stimulated respiration of isolated muscle mitochondria, and ADP-stimulated mitochondrial respiration in situ using saponin skinned muscle fibers. The in vitro maximal rates of respiration in isolated cardiac mitochondria from desmin-null and wild-type mice were similar. However, mitochondrial respiration in situ is significantly altered in desmin-null muscle. Both the maximal rate of ADP-stimulated oxygen consumption and the dissociation constant (K(m)) for ADP are significantly reduced in desmin-null cardiac and soleus muscle compared with controls. Respiratory parameters for desmin-null fast twitch gastrocnemius muscle were unaffected. Additionally, respiratory measurements in the presence of creatine indicate that coupling of creatine kinase and the adenine translocator is lost in desmin-null soleus muscle. This coupling is unaffected in cardiac muscle from desmin-null animals. All of these studies indicate that desmin IFs play a significant role in mitochondrial positioning and respiratory function in cardiac and skeletal muscle.

Disruption of muscle architecture and myocardial degeneration in mice lacking desmin.

Desmin, the muscle specific intermediate filament (IF) protein encoded by a single gene, is expressed in all muscle tissues. In mature striated muscle, desmin IFs surround the Z-discs, interlink them together and integrate the contractile apparatus with the sarcolemma and the nucleus. To investigate the function of desmin in all three muscle types in vivo, we generated desmin null mice through homologous recombination. Surprisingly, desmin null mice are viable and fertile. However, these mice demonstrated a multisystem disorder involving cardiac, skeletal, and smooth muscle. Histological and electron microscopic analysis in both heart and skeletal muscle tissues revealed severe disruption of muscle architecture and degeneration. Structural abnormalities included loss of lateral alignment of myofibrils and abnormal mitochondrial organization. The consequences of these abnormalities were most severe in the heart, which exhibited progressive degeneration and necrosis of the myocardium accompanied by extensive calcification. Abnormalities of smooth muscle included hypoplasia and degeneration. The present data demonstrate the essential role of desmin in the maintenance of myofibril, myofiber, and whole muscle tissue structural and functional integrity, and show that the absence of desmin leads to muscle degeneration.

Inhibition of desmin expression blocks myoblast fusion and interferes with the myogenic regulators MyoD and myogenin.

The muscle-specific intermediate filament protein, desmin, is one of the earliest myogenic markers whose functional role during myogenic commitment and differentiation is unknown. Sequence comparison of the presently isolated and fully characterized mouse desmin cDNA clones revealed a single domain of polypeptide similarity between desmin and the basic and helix-loop-helix region of members of the myoD family myogenic regulators. This further substantiated the need to search for the function of desmin. Constructs designed to express anti-sense desmin RNA were used to obtain stably transfected C2C12 myoblast cell lines. Several lines were obtained where expression of the anti-sense desmin RNA inhibited the expression of desmin RNA and protein down to basal levels. As a consequence, the differentiation of these myoblasts was blocked; complete inhibition of myoblast fusion and myotube formation was observed. Rescue of the normal phenotype was achieved either by spontaneous revertants, or by overexpression of the desmin sense RNA in the defective cell lines. In several of the cell lines obtained, inhibition of desmin expression was followed by differential inhibition of the myogenic regulators myoD and/or myogenin, depending on the stage and extent of desmin inhibition in these cells. These data suggested that myogenesis is modulated by at least more than one pathway and desmin, which so far was believed to be merely an architectural protein, seems to play a key role in this process.

Disseminated Geotrichum candidum infection in a patient with relapsed acute myelogenous leukemia following allogeneic stem cell transplantation and review of the literature.

We describe a woman with relapsed acute myelogenous leukemia after allogeneic stem cell transplantation who developed disseminated Geotrichum candidum infection during chemotherapy-induced neutropenia. The isolate was susceptible to voriconazole, amphotericin B, and micafungin in vitro. We review the literature regarding invasive infections with G. candidum, which predominantly affect immunocompromised hosts, and discuss potential therapies for this rare pathogen.

Cognitive neuroscience: the biology of the mind and findings and current opinion in cognitive neuroscience.

Cognitive Neuroscience: The Biology of the Mind by Michael Gazzaniga, Richard Ivry and George Mangun, W.W. Norton, 1998. £24.95 (xv+587 pages) ISBN 0 393 97219 4 Findings and Current Opinion in Cognitive Neuroscience by Larry Squire and Stephen Kosslyn, MIT Press, 1998. $35.00 (vii+381 pages) ISBN 0 262 69204 X.

Insights into blindsight.

Toward a science of consciousness (Tucson III): 27 April-2 May 1998, Tucson, Arizona, USA.

A polysomnographic and clinical report on sleep-related injury in 100 adult patients.

In 100 consecutive adults who came to a sleep disorders center complaining of repeated nocturnal injury, polysomnographic study identified five disorders: night terrors/sleepwalking (N = 54), REM sleep behavior disorder (N = 36), dissociative disorders (N = 7), nocturnal seizures (N = 2), and sleep apnea (N = 1). Ninety-five patients sustained ecchymoses, 30 had lacerations, and nine had fractures. DSM-III axis I disorders (past or current) were found in 48.1% of the group with night terrors/sleepwalking and in 30.6% of the group with REM sleep behavior disorder; these were mainly affective disorders. In these two groups, clonazepam controlled the symptoms of 51 of the 61 patients to whom it was given.

Integrating primary health care and mental health services--a successful rural linkage.

The local delivery of human services is currently receiving national emphasis. The expectation is that community-based services shall be provided with a minimum of duplication and with maximum efficiency, achieved partly by interdisciplinary and interorganizational cooperation. This emphasis was appropriately facilitated in the mid-1970s through the availability of the Mental Health Initiative grants. The grants, initiated by the Bureau of Community Health Services in conjunction with the National Institute of Mental Health, Public Health Service, promoted the increased availability of mental health services through formal linkages between community mental health centers and primary health care programs. One such successful linkage was between a small primary health care center and a nonfederally funded, multicounty, mental health center in northwest Illinois. Initiated in September 1980, the services of the linkage project included direct clinical mental health services delivered at the primary health care center site, consultation and education activities, and the coordination of interagency services. The project patients differed from the general clients of the mental health center in demographic characteristics, source of referral, and diagnoses. The key elements in successful linkages and the achievement of goals are analyzed. The experience of the linkage project is relevant to the 1980s. The project was prematurely ended after 14 months. Reduction in Federal funds severely cut support for the primary health care center, and the depressed local economy could not match the withdrawn Federal funds.

Maternal mortality in Europe.

Maternal mortality rates (or ratios) are widely used as one indicator of the quality of medical care. There has been concern that conclusions may be drawn from unreliable data. A survey of practices in European countries confirms that there are differences in interpretation of definitions and evidence of significant under-reporting in official returns of vital statistics. Actual and potential sources of error are identified and a need for greater precision and uniformity of data collection is established.

Fatal multiple drug intoxication following acute sertraline use.

A 53-year-old Caucasian male victim of suicide was suspected of overdose with sertraline and alprazolam after death-scene investigation. The concentration of sertraline, a selective serotonin reuptake inhibitor, was determined by a gas chromatograph with mass selective detection. The concentration of alprazolam, a triazolobenzodiazepine, was determined by high-performance liquid chromatography. The sertraline concentration was reported at 1.0 mg/L in peripheral blood, which is greater than previously reported in other postmortem cases in which death was attributed to a multiple drug overdose. The N-desmethylsertraline concentration was reported at 0.2 mg/L in peripheral blood, which is far less than in other postmortem cases and suggests acute intoxication in this case. The alprazolam concentration was reported at 33 microg/L in heart blood, which is within the therapeutic range. The cause of death was multiple drug intoxication following acute use of sertraline, the manner of death was suicide, and the mechanism of death is an unexplained drug interaction and/or toxicity.

Biopsy case mix and diagnostic yield at a Malawian central hospital.

Cancer is a major disease burden worldwide resulting in high morbidity and mortality. It is the leading cause of mortality in developed countries and is one of the three leading causes of death for adults in developing countries. Pathological examination of tissue biopsies with histological confirmation of a correct cancer diagnosis is central to cancer care. Without an accurate and specific pathologic diagnosis, effective treatment cannot be planned or delivered. In addition, there are marked geographical variations in incidence of cancer overall, and of the specific cancers seen. Much of the published literature on cancer incidence in developing countries reflects gross estimates and may not reflect reality. Performing baseline studies to understand these distributions lays the groundwork for further research in this area of cancer epidemiology. Our current study surveys and ranks cancer diagnoses by individual anatomical site at Queen Elizabeth Central Hospital (QECH) which is the largest teaching and referral hospital in Malawi. A retrospective study was conducted reviewing available pathology reports over a period of one full year from January 2010 to December 2010 for biopsies from patients suspected clinically of having cancer. There were 544 biopsies of suspected cancer, taken from 96 anatomical sites. The oesophagus was the most common biopsied site followed by breast, bladder, bone, prostate, bowel, and cervical lymph node. Malignancies were found in biopsies of the oesophagus biopsies (squamous cell carcinoma, 65.1%; adenocarcinoma, 11.6%), breast (57.5%), bladder (squamous cell carcinoma, 53.1%) and stomach (37.6%). Our study demonstrates that the yield of biopsy for clinically suspected malignancy was greater than 50% for the 11 most common sites and provides a current survey of cancer types by site present in the population reporting to our hospital.

Improving malaria control in West Africa: interruption of transmission as a paradigm shift

With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: (1) studies of the entire population (that are not restricted to children ≤5 or ≤10 years of age), (2) study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and (3) innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases.(AU)