Israel Medical Association Journal

The role of carbon in the development of life and as the structural backbone of all organisms is universally accepted and an essential part of evolution. However, the molecular basis is largely unknown and the interactions of carbon with nitrogen and oxygen in space are enigmatic. In 1985, the previously unknown form of carbon, coined fullerene, was discovered. We hypothesize that by virtue of the unique properties of fullerene, this hollow, ultra-robust, large, purely carbon molecule was the earliest progenitor of life. It acted as a stable universal biologic template on which small molecules spontaneously assembled and then formed, by further assembly, a surface mantle (here termed rosasome) of larger molecules. We submit that this process, by its inherent flexibility, initiated evolution, allowing the emergence of parallel diverse rosasome lines responding selectively to varying spatial environments. For example, rosasomal lines mantled with nucleotide and peptide layers are conceived as primordial forerunners of the ubiquitous ribosome. Moreover, the parallel independent and interdependent evolution of rosasome lines would be more rapid than sequential development, refute precedence of either DNA or RNA, and explain the evolution of integration of two subunits with different structures and functions in ribosomes and of the triplet nature of the codon. Based on recent astronomical data, this hypothesis supports the concept that life is not a singularity. This concept also suggests a potential vehicle for therapeutics, biotechnology and genetic engineering.

 Background: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates.

Objectives: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients.

Methods: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 ± 13 years treated with intravenous bisphosphonates.

Results: Most of the patients (n=44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 ± 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH)D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 ± 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 ± 191 ng/ml) but not with CTX levels (mean 0.265 ± 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99).

Conclusions: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.
 

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.
 

Background: Understanding the mechanism and the main components involved in rheumatic mitral regurgitation (MR) associated with dominant pliable mitral stenosis (MS) may improve our ability to repair some mixed rheumatic mitral valve pathologies.

Objectives: To assess mitral valve structural components in pure mitral stenosis versus mitral stenosis associated with mild regurgitation

Methods: Using two-dimensional echocardiography, we performed mitral valve structural analysis in two groups of patients prior to balloon mitral valvuloplasty (BMV). The first group, consisting of 13 females and 2 males (mean age 39 ± 5 years), suffered from pure pliable mitral stenosis (PPMS), while the second group, with 22 females and 2 males (mean age 44 ± 5 years), had mixed mitral valve disease (MMVD) characterized by mild MR in the presence of dominant pliable MS. All echocardiographic measurements relating to the mechanism of MR were undertaken during the systolic phase.

Results: The mean Wilkins scores of the PPMS and MMVD groups were 7 ± 1 and 8 ± 1 respectively (P = 0.004). No significant differences were found between the MMVD group and the PPMS group regarding annular circumference (15.5 ± 1.4 cm vs. 15.4 ± 1.6 cm, P = 0.84), annular diameter (36 ± 4 mm vs. 38 ± 5 mm, P = 0.18), and chordae tendinae length directed to the anterior mitral leaflet (AML) (10 ± 2 mm vs. 11 ± 2 mm, P = 0.137). However, anterior vs. posterior mitral leaflet length during systole was significantly lower in the MMVD than in the PPMS group (2.2 ± 0.5 vs. 2.8 ± 0.4, P = 0.02), whereas the AML thickness at the co-aptation point was greater in the MMVD than in the PPMS group (7 ± 1 vs. 5 ± 1 mm, P = 0.0004).

Conclusions: In rheumatic valves, thickening and shortening of the AML are the main factors determining the appearance of mild MR in the presence of dominant pliable MS.

The recent paper by Giubilini and Minerva suggesting the ethical permissibility of infanticide of normal newborns, calling it “postbirth abortion,” represents a dangerous deterioration of generally accepted ethical norms. Their proposal represents a clear example of the so-called slippery slope and we caution against abandoning the age-old traditions of the medical profession assigning intrinsic value to human life from birth. This article discusses the proposed concept, makes comparisons with earlier similar trends of thought, and highlights the dangers of the proposal.

Background: Acute, as opposed to chronic, anterior uveitis is rarely associated with macular or optic nerve  edema. Nevertheless, mild changes may not be visible on examination.

Objectives: To implement non-invasive ocular coherence tomography (OCT) for obtaining quantitative and qualitative data in the assessment of changes in macular morphology and peripapillary retinal nerve fiber layers in eyes with acute anterior uveitis.

Methods: This retrospective case-control study was conducted in patients with unilateral acute anterior uveitis lasting for up to one month. Patients with evidence of other ocular disease or who had undergone intraocular surgery were excluded. We reviewed the charts of 14 consecutive patients who were diagnosed with acute unilateral anterior uveitis between 2007 and 2008 at the Tel Aviv Medical Center. Data on demographic details, ophthalmic examination, macular thickness and peripapillary retinal nerve fiber layer (RNFL) thickness (as demonstrated by OCT) were retrieved. Retinal and RNFL thickness was compared between the healthy fellow eye (control) and the uveitic eye in the central and four perifoveal quadrant regions, and RNFL thickness was compared in the mean and four quadrant values by Student’s t-test.

Results: We evaluated 28 eyes of 7 males and 7 females (mean age 37.7 years, range 20–65). The diagnoses were: idiopathic in five patients, ankylosing spondylitis in five, Crohn’s disease in one patient and reactive arthritis in one. Nine patients were HLA-B27 positive. The retina and the peripapillary NFL in each area were thicker in the uveitic eyes compared to the controls. The difference was statistically significant. There was no correlation between the differences in OCT values and patients’ demographic characteristics.

Conclusions: OCT demonstrated that eyes with acute anterior uveitis had thicker maculae and thicker peripapillary RNFL than controls. This finding suggests that even milder anterior uveitis may be associated with some degree of posterior segment manifestations.

Background: Fatigue is a common complaint in primary care and has a broad differential diagnosis, making the approach complex and often ineffective.

Objectives: To follow the course of adults without a significant known background disease who complain of fatigue for the first time, and to characterize the family physician’s approach.

Methods: The study population comprised a random sample of 299 patients aged 18–45 who presented with fatigue as a first-time single complaint to their family physician. Excluded were patients with chronic diseases or states that may include signs of fatigue. We analyzed the index encounter data, the diagnostic and laboratory tests, the medications prescribed and the one year clinical outcome.

Results: Seventy percent were women, average age 30.5 years, and 69% had no known co-morbidities; 57% of the patients were physically examined at the first visit and most (78.6%) were sent for laboratory analysis. Five percent of laboratory tests were positive. Eighty patients (26.8%) were given a specific diagnosis, with the leading diagnoses being anemia and infectious diseases; 18.7% were given sick leave at the first visit. Fatigue was more common in early summer.

Conclusions: The majority of young healthy patients complaining of fatigue are not diagnosed with an organic physiological disorder. Many of the study patients were sent for laboratory tests but in most cases these tests were not contributory to the diagnosis or management. It seems likely that the most efficient strategy would be watchful follow-up with a minimum of testing.

The DRESS syndrome (drug reaction with eosinophilia and systemic symptoms), also known as DIHS (drug-induced hypersensitivity syndrome), presents clinically as an extensive mucocutaneous rash, accompanied by fever, lymphadenopathy, hepatitis, hematologic abnormalities with eosinophilia and atypical lymphocytes, and may involve other organs with eosinophilic infiltration, producing damage in several systems, especially kidney, heart, lungs, and pancreas. The pathogenesis is related to specific drugs (especially the aromatic anticonvulsants), altered immune response, sequential reactivation of herpes virus, and association with some HLA alleles. Glucocorticoids are the basis for the treatment of the syndrome, which may be given with intravenous immunoglobulin and, in selected cases, ganciclovir. This article reviews current concepts regarding the interaction of drugs, viruses and immune responses during this complex adverse-drug reaction.