Monitoring Immune Function During Immunosuppressive Therapy

Summary: Monitoring immune function during immunosuppressive therapy. J. B. Ziegler, Prudence Hansen, D. A. Cooper and R. Penny, Aust. N.Z. J. Med. , 1976, 6 , pp. 136–141.
Twenty-nine patients with a variety of connective tissue disorders were studied for the effects of immunosuppressive therapy on non-specific parameters of immune function. Baseline studies prior to therapy showed a frequent incidence of anergy (13%) lymphopenia (31%) and abnormal PHA response (43%). Despite these abnormalities in untreated patients it was possible to show an even higher incidence of anergy (31%), lymphopenia (66%) and abnormal PHA response (77%) following immunosuppressive treatment. The changes in lymphocyte count and PHA response were found to be statistically significant. It was found, paradoxically, that delayed hypersensitivity responses improved following institution of therapy in three patients. Clinical efficacy of immunosuppression correlated with lymphopenia and depressed PHA responses; in particular in the five patients with uncontrolled disease, these parameters were normal. Lymphocyte counts and PHA responses are the most simple and informative procedures to monitor immunosuppression in patients.     

Cardiac perforation following transcatheter PFO closure.

From December 1998 to August 2001, transcatheter closure of patent foramen ovale (PFO) with an Amplatzer PFO occluder has been successfully performed in our center in 102 patients without severe complications. We are reporting the first known case of cardiac perforation by an Amplatzer PFO occluder.     

Effect of micronized progesterone on bone turnover in postmenopausal women on estrogen replacement therapy

PURPOSE: To determine whether daily oral micronized progesterone affects bone turnover, as estimated by serum and urine biochemical markers, in postmenopausal women on long-term estrogen replacement therapy (ERT). METHODS: We recruited 14 women aged 65 or older to participate in a 9-week trial with micronized progesterone. Each woman had undergone a hysterectomy and was on unopposed ERT at time of study entry. Women received micronized progesterone 100 mg twice daily in the first week and then received 200 mg twice daily in weeks 2-9. We measured markers of bone turnover in serum and urine collected at baseline and at 3 weeks, 6 weeks, and 9 weeks on treatment. Markers of bone formation were serum bone alkaline phosphatase (BAP), N-terminal procollagen peptides (PINP), and osteocalcin (OC). Markers of bone resorption were urinary cross-linked N-terminal and C-terminal telopeptides of type I collagen. In addition, we measured serum progesterone, estradiol and sex hormone binding globulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL)-cholesterol levels at baseline and at 9 weeks on treatment. RESULTS: Mean serum progesterone levels increased from 1.6 +/- 1.1 to 15.2 +/- 3.9 ng/mL, which was within the luteal phase range (3-25 ng/mL). Crosslinked C-telopeptides of type I collagen and osteocalcin increased significantly (p < 0.05) with progesterone treatment, however, other bone markers did not change. Estradiol, estrone, and SHBG levels did not change with treatment. High-density lipoprotein-cholesterol levels decreased 19% (p < 0.001) at 9 weeks on treatment compared to baseline but total and low-density lipoprotein (LDL) cholesterol and triglycerides did not change with treatment. CONCLUSION: In postmenopausal women on long-term estrogen replacement therapy, micronized progesterone (400 mg/d) increased one marker each of bone resorption and bone formation. Other sensitive markers of bone turnover did not change with treatment. Further, micronized progesterone decreased HDL-cholesterol in these women. Our data do not support a beneficial effect of micronized progesterone on bone or cardiovascular risk factors in postmenopausal women.     

Identification of major and minor constituents of Harpagophytum procumbens (Devil's claw) using HPLC-SPE-NMR and HPLC-ESIMS/APCIMS

The HPLC-SPE-NMR technique, supported by HPLC-MS measurements, was used to determine structures of major as well as some minor constituents of ethanol and petroleum ether extracts of Harpagophytum procumbens (Devil's claw) roots. This method was also shown to be applicable for rapid and precise on-line identification of secondary metabolites present in commercial herbal products of H. procumbens. A total of 15 compounds (1-14 and 17) were identified from the ethanol and petroleum ether extracts, including a novel Diels-Alder dimer 14. Optimization of the HPLC-SPE-NMR experiments included quantitative (1)H NMR measurements, determination of trapping and elution efficiency, effect of multiple trapping of analytes, use of various deuterated solvents for SPE cartridge elution, and effect of post-column dilution ratio of eluent with water. Linear accumulation of apolar and relatively polar analytes was demonstrated for at least 8-10 repeated trappings, resulting in greatly improved signal-to-noise ratios in NMR spectra and reduced acquisition times. Thus, the HPLC-SPE-NMR technique provides an efficient means of identification of multiple components of crude extracts. By allowing on-line generation of high-quality 2D NMR data without traditional purification of extract components, the HPLC-SPE-NMR methodology represents a paradigm shift in natural products research with respect to structure elucidation.     

Rearrangements of immunoglobulin and TCR genes in lymphoid blast crisis of Ph + chronic myeloid leukaemia

Clonal rearrangements of immunoglobulin heavy chain genes as well as both T cell receptor (TCR) delta and gamma genes were found in four cases of blast crisis of Ph+ chronic myeloid leukaemia with unequivocal B cell precursor (common) immunophenotype. In one case, the TCR beta chain gene was also rearranged. Although the developmental sequence of TCR delta, gamma and beta rearrangements in T lymphocytes appeared to be respected, a full phenotypic effect, characteristic of T cell was not observed in these otherwise typical 'common' blast cells. Cytogenetic analysis ruled out the occurrence of TCR rearrangement due to structural chromosome changes. A high incidence of unexpected TCR gene rearrangements has been previously reported in the de novo 'common' acute lymphoblastic leukaemias (ALL). Our cases of chronic myeloid leukaemia (CML) in lymphoid blast crisis show that genotypic similarities may exist between these two haematological entities.     

Endocrine tumors of the pancreas.

Neuroendocrine tumors of the pancreas are rare neoplasms of the heterogeneous group of neuroendocrine gastroenteropancreatic tumors that originate from totipotential stem cells or preexisting endocrine cells within the pancreas. Most neuroendocrine tumors of the pancreas are benign or show an indolent course of disease.A subset of them shows a very aggressive behavior, becomes highly malignant, and metastasizes early with life-limiting consequences. An effective disease-management includes the diagnostic approach with hormonal testing and localization and surgical treatment with histologic classification in combination with biotherapy, chemotherapy, or therapy with radionucleotides, de-pending on the individual behavior of the tumor. The primary goal is the improvement of symptoms leading to an acceptable quality of life in the individual patient.