Circulating levels of midregional parathyroid hormone-related protein in hypercalcaemia of malignancy

OBJECTIVE: We have developed and evaluated a sensitive radioimmunoassay directed against the midregional part of parathyroid hormone-related protein (PTHrP), which is involved in the syndrome of humoral hypercalcaemia of malignancy. PATIENTS: Midregional PTHrP levels were studied in 41 consecutive inpatients with malignancy and hypercalcaemia, 32 normocalcaemic patients with malignancy, 21 patients with primary hyperparathyroidism, 34 patients with renal failure, and 87 normals. MEASUREMENTS: The assay used an antiserum against the midregional amino acid residues 53-84 of PTHrP and PTHrP(1-86) as label and standard. Midregional PTHrP was stable in serum and plasma and could be measured directly without sample extraction. RESULTS: Normal plasma concentrations ranged from undetectable (< 5 pmol/l) to 21 pmol/l. In renal failure, PTHrP was positively correlated with serum creatinine, but PTHrP elevations of up to 30 pmol/l were found only in severe renal dysfunction with creatinine > 850 mumol/l. In hypercalcaemia caused by solid tumours, midregional PTHrP was elevated in 81% (22 of 27) of patients, ranging from undetectable to 203 pmol/l (median: 40 pmol/l). In these patients serum calcium correlated positively with PTHrP (P < 0.01). Mean PTHrP levels were indistinguishable in subgroups with and without metastatic skeletal disease. The mechanism of hypercalcaemia in 14 patients with haematological malignancy was apparently different, since all but one had normal or only marginally elevated PTHrP levels. In 21 patients with primary hyperparathyroidism midregional PTHrP was normal in 20. The assay was therefore especially useful in distinguishing the latter condition from humoral hypercalcaemia of malignancy as the second major cause of hypercalcaemia. PTHrP was normal in all 32 patients with normocalcaemic malignancy. CONCLUSION: This radioimmunoassay of midregional PTHrP provides high diagnostic sensitivity in the identification of humoral hypercalcaemia of malignancy caused by solid tumours. The assay should therefore be useful in the differential diagnosis of hypercalcaemia.     

Pathways of NH3/NH 4 + permeation across Xenopus laevis oocyte cell membrane

While acid loading with extracellular NH₄Cl solutions usually first alkalinizes the cells through NH₃ influx, and acidifies only when NH₄Cl is removed, Xenopus oocytes became immediately acidic upon NH₄Cl addition and the cells did not acidify further upon its removal. Since NH₄Cl solutions also collapsed the membrane potential (V _m) and resistance (R _m), we conclude that primarily NH ₄ ⁺ entered the cells where it liberated H⁺, with NH₃ being trapped in intracellular lipid stores. To identify the NH ₄ ⁺ permeation pathway we have used K⁺ channel blockers (Ba²⁺, Cs⁺, tetraethylammonium, quinidine), various cation transport inhibitors (ouabain, bumetanide, amiloride) and other inhibitors, some of which block non-selective cation channels (La³⁺, diphenylamine-2-carboxylate, and p-chloromercuribenzoate). However, only the latter substances partially prevented the collapse of V _m and R _m. This suggests, that NH ₄ ⁺ passes through non-selective cation channels. In accordance with the voltage dependence and/or stretch activation of such channels NH ₄ ⁺ fluxes appeared to be asymmetric. NH ₄ ⁺ influx, which depolarized and swelled the cells, was large and acidified rapidly, while the efflux, which repolarized and shrank the cells, was slow and alkalinized only slowly.     

Three years with a national apheresis registry

The large number of unsolved problems in plasma exchange therapy makes an apheresis registry appear useful. The results of such an open prospective observational study from 1987 to 1989 in East Germany are presented in this paper. With 1,945 procedures in a total of 419 patients (on average 4.1 treatments per patient) about 80% of all treatments in the country were registered. Exchange volume averaged 2.7 (± 0.78) 1 or 43 (± 13.9) ml/kg body weight. Substitutes were albumin (51% of the cases), FFP (22%), and both (22%), Nephrological (25%) and neurological (23%) diagnoses prevailed among the treated diseases. Haematologic diseases (12%) were underrepresented and hepatic coma (20%) was overrepresented. Minor side effects occurred in 22% of all treatments and severe complications in 38 treatments (2%). Four fatalities probably resulted from plasmapheresis therapy. The registry permits an assessment of the treatment results and of several trends during the period of observation. © 1992 Wiley-Liss, Inc.     

Diagnostic techniques: Three-dimensional ultrasound in obstetrics and gynaecology: technique, possibilities and limitations

Three-dimensional (3D) ultrasound offers several options extendingconventional two-dimensional scanning. Various imaging modesare available. Three perpendicular planes displayed simultaneouslycan be rotated and translated in order to obtain accurate sectionsand suitable views needed for diagnosis and geometric measurements.3D ultrasound, tomography combines the advantages of ultrasound,e.g. safety, simplicity of application and inexpensiveness,with the advantages of sequentially depictable sections in numerousrotatable and translatable sections. Surface rendering givesdetailed plastic images if there are surrounding layers of differentechogenicity allowing for the definition of a certain threshold.Transparent modes provide an imaging of structures with a higherechogenicity in the interior of the object. A combination ofthe two modes sequentially definable by the sonographer allowsfor the optimal viewing of structures. These imaging modes areinnovative features which have to be evaluated for clinicalapplicability and usefulness. Digital documentation of wholevolumes enables full evaluation without loss of informationat a later point. 3D technology provides an enormous numberof technical options which have to be evaluated for their diagnosticsignificance and limitations in obstetrics and gynaecology.     

Exocrine pancreatic function in children with systemic lupus erythematosus.

We examined the incidence and spectrum of pancreatic disease in pediatric systemic lupus erythematosus (SLE). We measured serum immunoreactive cationic trypsinogen (IRT) in 185 samples obtained from 35 patients with SLE. Fifteen patients (43%) had elevated IRT levels on at least one occasion. Serum samples were obtained in 20 of 35 patients before start of treatment. Seven of these 20 patients (35%) had elevated IRT levels at diagnosis, which slowly returned to normal as their disease was controlled with treatment. A further 3 of these 20 patients in whom we had sera at diagnosis had elevated levels at some course during their illness. Of the remaining 15 patients in whom sera was not available at diagnosis, 5 patients had increased IRT levels on at least one occasion. We show that elevated IRT levels are common in pediatric SLE, but there was no apparent association with drugs such as prednisone and azathioprine. However, high levels of IRT at the time of diagnosis may be related to an underlying disease component such as vasculitis.     

Protection with Antibody to Tumor Necrosis Factor Differs with Similarly Lethal Escherichia coli versus Staphylococcus aureus Pneumonia in Rats

Background: Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia.

Methods: Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h.

Results: Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P >= 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6;P = 0.006) and S. aureus (-0.5 +/- 0.04;P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P <= 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003).     

Kidney transplantation in the cyclosporine era

Seventy-seven patients underwent transplantation, using a cyclosporine-prednisone immunosuppression protocol. No recipients died, and graft survival at one year was 100% for living related donor (LRD) recipients and 84% for cadaver donor (CD) recipients. Nineteen percent of locally harvested, flush-cooled kidney recipients required dialysis, whereas imported kidneys had a 66% dialysis rate. Infectious complications occurred in 17% of patients. Mean hospitalization was 12.8 days for LRD recipients and 13.6 days for CD recipients. Twenty-eight patients required 37 readmissions, mostly for treatment of rejection and infections. Total two-year cost for LRD transplants was +21,400; for CD transplants, +23,900.