Delayed neurologic display in murine typhus. Report of two cases.

Two cases of murine typhus with prolonged neurologic manifestations appearing after the febrile stage of the illness are described. One patient had behavioral and memory disturbances for almost 18 months after defervescence, which terminated gradually without specific therapy. The second patient had similar manifestations over a period of weeks that rapidly resolved after tetracycline therapy. Such phenomena were not previously described in the literature, as far as we know, although similar manifestations were noted in Rocky Mountain spotted fever.

ATF3-dependent cross-talk between cardiomyocytes and macrophages promotes cardiac maladaptive remodeling.

RATIONALE: Pressure overload induces adaptive remodeling processes in the heart. However, when pressure overload persists, adaptive changes turn into maladaptive alterations leading to cardiac hypertrophy and heart failure. ATF3 is a stress inducible transcription factor that is transiently expressed following neuroendocrine stimulation. However, its role in chronic pressure overload dependent cardiac hypertrophy is currently unknown. OBJECTIVE: The objective of the study was to study the role of ATF3 in chronic pressure overload dependent cardiac remodeling processes. METHODS AND RESULTS: Pressure overload was induced by phenylephrine (PE) mini-osmotic pumps in various mice models of whole body, cardiac specific, bone marrow (BM) specific and macrophage specific ATF3 ablations. We show that ATF3-KO mice exhibit a significantly reduced expression of cardiac remodeling markers following chronic pressure overload. Consistently, the lack of ATF3 specifically in either cardiomyocytes or BM derived cells blunts the hypertrophic response to PE infusion. A unique cross-talk between cardiomyocytes and macrophages was identified. Cardiomyocytes induce an ATF3 dependent induction of an inflammatory response leading to macrophage recruitment to the heart. Adoptive transfer of wild type macrophages, but not ATF3-KO derived macrophages, into wild type mice potentiates maladaptive response to PE infusion. CONCLUSIONS: Collectively, this study places ATF3 as a key regulator in promoting pressure overload induced cardiac hypertrophy through a cross-talk between cardiomyocytes and macrophages. Inhibiting this cross-talk may serve as a useful approach to blunt maladaptive remodeling processes in the heart.

Relapse of rickettsial Mediterranean spotted fever and murine typhus after treatment with chloramphenicol.

In the years 1975-1984, 132 patients with rickettsial Mediterranean spotted fever and murine typhus were treated with chloramphenicol or tetracycline. Among the 24 patients who received chloramphenicol ten relapsed and one failed to respond at all. None of the 108 recipients of tetracycline suffered a relapse. It appears that tetracycline should serve as first-line therapy in several rickettsial diseases.

Hyporeninemic hypoaldosteronism associated with multiple myeloma: 11 years of follow-up.

Hyporeninemic hypoaldosteronism is an important underlying condition, causing hyperkalemia with hyperchloremic metabolic acidosis, disproportionate to the degree of renal insufficiency present. The principal defect in this syndrome is a reduced level of plasma renin activity, which results in secondary hypoaldosteronism. Diabetes mellitus is usually the primary underlying renal disease, though other causes of renal diseases associated with this syndrome have been described. This case report describes for the first time an elderly patient with multiple myeloma, in remission for more than 11 years, associated with the syndrome of hyporeninemic hypoaldosteronism at the time of diagnosis. The complete resolution of the syndrome after vigorous chemotherapy is an intriguing possibility.

Brucellosis of the spine. A report of 3 cases.

Three cases of spinal osteomyelitis due to brucellosis are reported, all in women. Radiological confirmation was delayed for at least three months after the first clinical manifestation, while in one patient a bone scan was positive at an early stage. In two of the three cases the diagnosis was delayed because of insufficient awareness of the disease. Spinal osteomyelitis caused by Brucella is indistinguishable radiologically from that caused by other micro-organisms and needle aspiration or exploration is frequently performed to establish the correct diagnosis. Increased awareness of brucellosis and the carrying out of appropriate blood cultures and serological tests may make these procedures unnecessary.

Drug-induced post-surgical haemorrhage resulting from trimethoprim-sulphamethoxazole. A case report.

A case of life-endangering post-operative haemorrhage due to thrombocytopenia resulting from administration of trimethoprim-sulphamethoxazole is described. Withdrawal of the drug led to complete recovery. This side effect should be kept in mind, especially in patients scheduled for surgical intervention. As thrombocytopenia may develop insidiously and gradually, it is highly recommended to perform full blood tests immediately prior to surgery and repeat them in the post-operative period.

Treatment-induced host-mediated mechanisms reducing the efficacy of antitumor therapies.

In addition to its direct effects on tumor cells, chemotherapy can rapidly activate various host processes that contribute to therapy resistance and tumor regrowth. The host response to chemotherapy consists of changes in numerous cell types and cytokines. Examples include the acute mobilization and tumor homing of pro-angiogenic bone marrow-derived cells, activation of cells in the tumor microenvironment to produce systemic or paracrine factors, and tissue-specific responses that provide a protective niche for tumor cells. All of these factors reduce chemotherapy efficacy, and blocking the host response at various levels may therefore significantly improve treatment outcome. However, before the combination of conventional chemotherapy with agents blocking specific aspects of the host response can be implemented into clinical practice, a better understanding of the molecular mechanisms behind the host response is required.

Rickettsial infection of the central nervous system: the role of prompt antimicrobial therapy.

Rickettsial diseases of man, which are prevalent in all the continents (except Antartica) continue to be a major health problem in tropical and temperate parts of the world. Rickettsioses must be considered in every traveller seeking medical attention soon after returning from endemic areas, since the disease can be associated with significant morbidity. When a definite diagnosis has been made by specific serological tests, prompt antimicrobial therapy is indicated. A tetracycline should be regarded as the drug of choice due to its high efficacy, low toxicity, superior in vitro activity and the possibility of relapse which can follow chloramphenicol therapy.

Primary pneumococcal peritonitis in patients with cardiac ascites: report of 2 cases.

Two patients with fatal spontaneous pneumococcal peritonitis associated with ascites due to severe heart failure are reported. Remarkable clinical features included gradual onset and absence of fever and signs of peritonitis. Only 1 case of spontaneous bacterial peritonitis associated with cardiac ascites was described previously and was caused by enterococcus.

Q fever meningoencephalitis associated with bilateral abducens nerve paralysis, bilateral optic neuritis and abnormal cerebrospinal fluid findings.

Q fever is an zoonosis caused by Coxiella burnetti, the clinical features of which are often nonspecific and self-limited. Involvement of the central nervous system is rare and is usually seen as a complication of endocarditis caused by this rickettsial organism in the chronic disease. Specific neurological manifestations in the course of the acute illness aseptic meningitis, encephalitis, toxic confusional states, extrapyramidal signs, dementia and behavioral disturbances. We describe a patient who developed reversible bilateral abducens nerve paralysis and bilateral optic neuritis in the course of acute Q fever meningoencephalitis.

Dental infection as the cause of pyrexia of unknown origin--two case reports.

Two cases of pyrexia of unknown origin are described in which no cause was found despite exhaustive inpatient investigation until occult dental infection was detected: extraction of the teeth involved was followed by resolution of the pyrexia. Dental infection should be considered as an unusual but eminently treatable cause of pyrexia of unknown origin.

Involvement of the kidneys in Mediterranean spotted fever and murine typhus.

We reviewed 58 patients, 27 with murine typhus (MT) and 31 with Israeli Mediterranean spotted fever (IMSF), hospitalized at the Sheba Medical Center 1979-1988. Five patients with MT and five with IMSF had evidence of renal impairment. One patient with MT underwent a renal biopsy, and two patients with IMSF died and had autopsy examinations with histology of the kidney. The principal histopathological lesion found in those most severe cases of rickettsiosis-induced renal failure was multifocal perivascular interstitial nephritis. In contrast with previous reports, involvement of the kidneys in rickettsial infection seems to be relatively common. Early diagnosis and treatment with hydration and specific antimicrobial agents is mandatory to prevent morbidity.