LOW-DOSE MAINTENANCE CLOZAPINE TREATMENT IN THE PROPHYLAXIS OF BIPOLAR AFFECTIVE DISORDER

SUMMARY A chronically relapsing middle-aged man with bipolar affective disorder responded poorly to different forms of conventional pharmacotherapy, including depot antipsychotic medication and lithium. The addition of clozapine to lithium, even at doses as low as 25mg/day, led to a stabilisation of his mood. The withdrawal of low-dose clozapine led to a relapse within a few days. It is concluded that maintenance low-dose clozapine should be considered in bipolar disorders resistant to other treatments.     

Neurofibromatosis 1 with pheochromocytoma

Von Hippel-Lindau (VHL) disease includes a wide spectrum of highly vascular tumors like pheochromocytoma, cysts and adenomas of the pancreas and kidney, endolymphatic sac and renal cell carcinoma. Molecular analysis of the VHL gene is vital in these patients and their kindred. Neuroendocrine pancreatic tumors are rare and are known for their malignant and metastatic potential. We discuss an interesting case of a young lady who had a strong family history of central nervous system and spinal tumors. Our patient presented with recently detected severe hypertension. She was found to have elevated urinary normetanephrine levels; radiological imaging revealed bilateral pheochromocytomas with a pancreatic lesion. On genetic analysis, a variation, c.IVS 2 + 3 A > G, was found in the intronic region following exon 2 of the VHL gene. This variant appears novel. This patient underwent bilateral adrenalectomy (right total and left cortical sparing), distal pancreatectomy and splenectomy. Histology was diagnostic for pheochromocytoma with a neuroendocrine tumor of the pancreas. The postoperative period was uneventful. She was advised genetic screening of all her first-degree relatives.     

Profile of live-born infants of in-vitro fertilisation

Introduction: The Army Hospital (R&R) is the only service hospital providing in-vitro fertilisation (IVF) facility. Neonatal characteristics of live-born infants at this centre over a two-year period are analyzed in this study.     

<Emphasis Type="Italic">FGFR1</Emphasis> amplification in breast carcinomas: a chromogenic <Emphasis Type="Italic">in situ</Emphasis>hybridisation analysis

Background  

The amplicon on 8p11.2 is reported to be found in up to 10% of breast carcinomas. It has been demonstrated recently that this amplicon has four separate cores. The second core encompasses important oncogene candidates, including the fibroblast growth factor receptor 1 (FGFR1) gene. Recent studies have demonstrated that specific FGFR1 amplification correlates with gene expression and that FGFR1 activity is required for the survival of a FGFR1 amplified breast cancer cell line.     

EICOSAPENTAENOIC ACID IN TREATMENT-RESISTANT DEPRESSION ASSOCIATED WITH SYMPTOM REMISSION,STRUCTURAL BRAIN CHANGES AND REDUCED NEURONAL PHOSPHOLIPID TURNOVER

The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine months later. The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically. During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover. Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.     

Microinfarction as a result of hypertension in a primate model of cerebrovascular disease

Ten adult cynomolgus monkeys were studied as a non-human primate model of hypertensive cerebrovascular disease. Seven were made hypertensive by surgical coarctation of the aorta and three served as unoperated controls. After survival periods of 8–30 months, the brains were serially sectioned and surveyed for neuropathological changes. The most conspicuous change was minute areas of microinfarction in the white and gray matter. The lesions were of irregular shape with an average maximum diameter of less than 0.5 mm. They were slightly larger in the gray than in the white matter and appeared to be of different ages. Their area of predilection was the white matter of the forebrain, with smaller numbers in the cerebral cortex and scattered lesions elsewhere in the forebrain, brain stem and cerebellum. These microinfarcts did not correspond to usually described lesions in the human brain in hypertension or in other animal models of hypertensive cerebrovascular disease. We suggest that they represent an early change in the natural history of hypertensive neuropathology. Received: 1 September 1998 / Revised: 12 January 1999, 9 February 1999 / Accepted: 10 February 1999     

Systemic monoclonal antibody therapy for eliminating minimal residual leukemia in a rat bone marrow transplant model

In an animal bone marrow transplant (BMT) model that mimics the human clinical condition, we evaluated the effectiveness of monoclonal antibody (MoAb) therapy in eliminating minimal residual disease (MRD) in a leukemic host. Leukemic rats were prepared with marrow ablative but noncurative doses of busulfan (BU) and cyclophosphamide (CY). Two days after syngeneic BMT, rats were treated with MoAb. Although all control rats died of leukemia relapse, 58% of those treated with MoAb were cured without any demonstrable effect on the rate of peripheral blood leukocyte recovery. Furthermore, the level of complement, an important effector in suppressing leukemia proliferation in the normal rat, was not adversely affected by BU/CY, BMT and MoAb. Thus, we demonstrated in an animal model that MoAb therapy may be a useful, nontoxic adjunct to high-dose chemotherapy and BMT in eliminating MRD.