Severe hyponatremia and diabetes insipidus caused by low-dose cyclophosphamide in breast cancer patients: A case report and literature review.

RATIONALE: Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is uncommon, it can lead to serious complications and even death. PATIENT CONCERNS: A 44-year-old woman with left-sided breast cancer suddenly experienced headaches, disorientation and weakness after receiving low-dose neoadjuvant chemotherapy combined with CTX and doxorubicin. DIAGNOSES: The patient pathology showed invasive breast carcinoma. She developed severe hyponatremia and a generalized seizure after completing the first cycle of neoadjuvant chemotherapy with CTX and doxorubicin. Laboratory tests showed a serum sodium of 118 mmol/L (normal range 135-145 mmol/L) and potassium sodium 3.16 mmol/L (normal range 3.5-5.5 mmol/L). Subsequently, the patient developed secondary diabetes insipidus 4 hours after sodium supplementation, her 24-hour urine volume was 4730 mL (normal range 1000-2000 mL/24 hours), and the urine specific gravity decreased to 1.005. INTERVENTIONS: The patient was given intravenous sodium chloride (500 mL of 3%NaCl, 100 mL/hour) and potassium chloride (500 mL of 0.3%KCl, 250 mL/hour). Meanwhile, she was advised to reduce her water intake, and pituitrin was administered to prevent dehydration caused by diabetes insipidus. OUTCOMES: The patient completely recovered after correcting of the serum sodium concentration (137 mmol/L) without any neurological deficits. After discontinuing pituitrin, her 24-hour urine volume was 2060 mL and the urine specific gravity was 1.015. LESSONS: This is a typical case of severe hyponatremia induced by low-dose CTX. Clinicians and healthcare providers should be aware of this potential toxicity, and appropriate monitoring should be implemented.

Mast cell activation in the acupoint is important for the electroacupuncture effect against pituitrin-induced bradycardia in rabbits.

This research was conducted to verify the structural and functional characteristics of mast cells in the electroacupuncture (EA) effects on bradycardia. First, we examined the mast cell density at PC 6, adjacent acupoint LU 7, and a non-acupoint. We tested the effects of EA at PC 6 on heart rate (HR) and blood pressure (BP) in rabbits with pituitrin-induced bradycardia. We also injected sodium cromolyn (Cro), a mast cell membrane stabilizer, at PC 6 30 min before EA to investigate if it affected the EA effects. The results showed that in both PC 6 and LU 7, the mast cell densities were higher than in the non-acupoint (P < 0.05). EA could induce mast cell degranulation at PC 6, which could be suppressed by sodium cromolyn (P < 0.05). EA improved HR, though the change was relatively small in the initial stage with a significant change at 35 min after modelling (P < 0.05). BP significantly improved at 10 min after the onset of pituitrin-induced bradycardia (P < 0.05). The EA effects on both HR and BP were suppressed by sodium cromolyn (P < 0.05). Therefore, we concluded that mast cells in the acupoint are important for the EA effects against pituitrin-induced bradycardia in rabbits.

Osmotic demyelination syndrome after correction of severe hyponatremia associated with pituitrin.

Osmotic demyelination syndrome (ODS) may be precipitated by aggressive correction of a hypoosmolar state. We report the case of a 24-year-old woman who developed ODS during rapid correction of asymptomatic hyponatremia caused by pituitrin prescribed for hemoptysis. After hyponatremia correction by NaCl supplementation, the patient developed limb weakness, blurred vision, hand and perioral numbness, and lisp. Magnetic resonance imaging (MRI) revealed bilateral signal hyperintensity of the globus pallidus and caudate nucleus, compatible with extra-pontine ODS. These symptoms improved gradually with treatment, and brain MRI ~ 3 months later indicated substantial resolution of ODS. This case serves as a warning to physicians that hypoosmotic correction must be achieved at a controlled rate.

Extrapontine myelinolysis associated with pituitrin: case report and literature review.

BACKGROUND: Hyponatremia is the most common electrolyte abnormality encountered in hospitalized patients, resulting from a varied spectrum of conditions. Both the primary disturbance and its correction can result in life-threatening neurological consequences. Extrapontine myelinolysis is one such complication that is associated with the rapid correction of hyponatremia. Here we describe a patient who developed extrapontine myelinolysis unexpectedly after the correction of hyponatremia, which involved the drug pituitrin. CASE PRESENTATION: A 24-year-old Chinese woman was transferred to our neurology department with the symptoms of dysarthria and quadriparesis developing one day after the correction of hyponatremia (from 118 mmol/L to 140 mmol/L), which followed with a continuous intravenous drip of pituitrin used to control hemoptysis in the emergency room. During the course, she developed involuntary movement. Magnetic resonance imaging changes were consistent with extrapontine myelinolysis. CONCLUSION: This present case describes the mechanism of profound hyponatremia involving pituitrin, and the subsequent development of extrapontine myelinolysis. Physicians may approach effective clinical management of patients through awareness of the adverse effect of pituitrin on serum sodium levels, and avoid rapid correction of hyponatremia in clinical practice.

Effect of Coherin™ on intraocular pressure, pupil size and heart rate in the glaucomatous Beagle: a pilot study.

OBJECTIVE: To evaluate effects of Coherin™ on intraocular pressure (IOP), pupil size (PS), and heart rate (HR) in glaucomatous Beagles in single-dose studies in a pilot study. MATERIALS AND METHODS: Intraocular pressure, PS, and HR were measured in eight glaucomatous Beagles. One randomly chosen eye received single 50 µL doses of differing concentrations of Coherin™ (treated eye) or vehicle (placebo-treated eye), and the fellow eye served as the untreated control. After the first measurements, a single dose of either Coherin™ or sterile water vehicle was instilled in the drug and placebo eyes, respectively. RESULTS: The mean ± SEM diurnal changes in IOP after 0.005%, 0.01%, 0.2%, 0.284%, 1%, 2%, and 4% topical Coherin™ once daily were 7.6 ± 3.2 mmHg, 15.5 ± 5.3 mmHg, 11.2 ± 4.4 mmHg, 11.8 ± 4.4 mmHg, 19.1 ± 3.8 mmHg, 5.0 ± 1.8 mmHg, and 8.8 ± 2.8 mmHg, respectively. The declines in IOP were significantly different (P < 0.05) from the untreated control eyes with the 0.2% and 0.284% Coherin™-treated eyes and suggestive for 1% Coherin™ concentrations. No signs of irritation, significant PS, and HR changes were detected in the Coherin™-treated eyes. CONCLUSION: Of seven different concentrations, 2% and 0.248% Coherin™ produced significant declines in IOP in the glaucomatous beagle in single-dose studies when compared to both untreated control and placebo-treated eyes. One percent Coherin™ solution produced significant IOP decreases compared with the placebo-treated eye but not the untreated control eyes. No local ocular irritation, PS and HR changes were observed in Coherin™-treated eyes. This pilot study suggests that topical Coherin™ has potential as an ocular hypotensive agent.

[Hypothalamic syndromes after the administration of toxic doses of drugs for terminating pregnancy]. / O gipotalamicheskikh sindromakh posle primeneniia toksicheskikh doz lekarstvennykh sredstv s tsel'iu prekrashcheniia beremennosti.

Twenty-five women presented with primary injuries of the hypothalamic area and the hypothalamic syndrome that resulted from the intake of toxic doses of drugs (TDD) for inducing an abortion. The situation was simulated in mature rats. Experiments evidenced a predominant involvement of the hypothalamic area, vs. other portions of the brain. All the patients developed the vegetovascular form of the hypothalamic syndrome, combined with neuroendocrine and thermoregulation disturbances. TDD-induced increase of the vulnerability of the hypothalamus during pregnancy may be explained by structural and functional peculiarities of the female hypothalamus, by suppression of the dominant gestational functional integrating system formed during pregnancy and simultaneous failure of the principal performance system, the hypothalamus.

PIP: An experiment on intake of toxic doses of drugs (TDD) was conducted in Russia on 27 mature white rats divided into 3 groups. The 1st group was given intramuscular injections of synestrol (10-15 mg/kg), pituitrin (5 mg/kg), pachycarpine (40-50 mg/kg) and quinine (200 mg/kg) outside the pregnancy phase. The 3rd group was in the pregnancy phase and given the same doses of these drugs. The 2nd group was in the pregnancy phase and not given these preparations. The control group consisted of 4 rats injected with a physiological solution in the amount of 2 mg/kg. The preparations were given over a 5-day period. After decapitation, the anterior and posterior sections of the hypothalamus and cerebral cortex were analyzed. It showed that structural and metabolic changes in the rats of the 1st group were represented equally both in the cerebral cortex and in the hypothalamic area. In the 3rd group, these changes were considerably greater in hypothalamic area than in the cerebral cortex. In the 2nd group, only minor metabolic changes were observed in the hypothalamic area, apparently caused by the pregnancy itself. All this proves that injection of TDD during pregnancy primarily affects the hypothalamic area. Twenty-five women with affection of the hypothalamic area, developing as a result of TDD intake (synestrol, pituitrin, pachycarpine and quinine) to terminate pregnancy. Duration of intake was 2-5 days. Clinical investigations, EEG's, cranial x-rays, and examination of the fundus of the eye and conditions of the autonomic nervous system were conducted on all the women. An autonomic-vascular form of hypothalamic syndrome was noted in all the patients, in all cases combined with minor neuroendocrine and thermoregulation disturbances. There also were observed innervation impairment of cranial nerves, changes in muscle tone, and asymmetry of deep reflexes. Hypertension syndrome was also determined in a number of cases. The emotional disorders which are typical of patients suffering from primary affection of the hypothalamic area should also be noted. Hypothalamic syndrome in the women did not develop immediately after taking TDD, but 2 weeks to 2 months later. There is reason to believe that during the pregnancy there is a heightened "vulnerability" of the hypothalamus as a result of changes in its functional state and activities. Intake of TDD to interrupt a pregnancy disturbs the activities of the hypothalamus and also the limbic system as a whole. The activities of the gestational integrative functional system are especially important during pregnancy. Intake of TDD results in structural and functional failure of the gestational functional system and its principal performance organ--the hypothalamus.

Mediastinal and retroperitoneal fibrosis with fibrotic pulmonary nodules: a case report.

We report a patient with a long history of pan-hypopituitarism treated with pituitary snuff who developed superior mediastinal fibrosis involving the visceral pericardium, retroperitoneal fibrosis, and a peculiar widespread nodular fibrosis of the lungs.

[Pituitary gland extract insufflation lung]. / Hypophysenextraktschnupferlunge.

In two patients with diabetes insipidus the development of an allergic alveolitis with transition into pulmonary fibrosis could be observed. The alveolitis is evoked by snuffing of posterior pituitary extracts. The pathomechanism of this side effect (disease) is similar to those of other allergic alveolitides (e.g. farmer's lung, bird-fancier's lung, malt-worker's lung etc). This disease can be avoided by changing the therapy of diabetes insipidus to fully synthetic preparations free of protein. When irreversible changes are already present at the stroma of the lung (X-ray picture, function of the lung, histology), then the therapeutic possibilities are restricted and the prognosis is unfavourable.

[Drug-induced lung diseases]. / Medikamentös bedingte Pneumopathien.

Drug-induced lung diseases may present themselves as bronchial reactions (e.g. bronchial asthma), diseases of the parenchyma (e.g. pulmonary infiltrates with eosinophilia, diffuse fibrosing alveolitis), of the pulmonary vasculature (vasculitis) and of the pleura (e.g. pleurisy or pleural fibrosis). Pathogenetically the two most pertinent types of reaction are hypersensitivity or toxic reactions, and less often biologic reactions such as opportunistic infections after cytotoxic and immunosuppressive therapy. Many drug-induced respiratory diseases are reversible upon withdrawal of the offending agent; others may be irreversible or even progress.

The physiologic properties and therapeutic potential of coherin.

Coherin, a peptide isolated from the bovine neurohypophysis, has been shown to be an effective therapeutic agent in post-gastric surgery physiologic obstruction and regional ileitis. Of twenty-four patients with post-gastric surgery physiologic obstruction, coherin relieved symptoms in twenty-three, a 96 per cent efficacy rate. The efficacy of coherin with ileitis was based on the fact that ten of twenty-seven patients treated have required coherin on a continuing basis to stay functional. These patients have requested coherin treatment for an average of five years each, and have each on multiple occasions tried to discontinue coherin treatment with prompt return of symptoms and cessation of symptoms when coherin was reinstituted. All of the ileitis patients had previously failed to respond to standard and usual medical treatment.