Impaired glucose tolerance coincides with abnormal release of growth hormone following a glucose load as well as in response to TRH in acromegaly

It is known that some acromegalic patients exhibited a paradoxical release of growth hormone (GH) after glucose administration. We have attempted to investigate a relationship between the paradoxical GH secretion with the abnormal glucose tolerance test present in some cases of acromegaly. We also studied the inappropriate increase in GH levels following thyrotropin releasing hormone (TRH) injection which is present in some acromegalics. We found that only those patients who had an abnormal glucose tolerance test exhibited simultaneously, the paradoxical release of GH, moreover, the same patients showed GH release following TRH administration. This observation suggests that some acromegalics have an abnormality in their hypothalamic glucose receptor and such abnormality is associated with abnormal GH secretion when TRH is administered. On basis of these findings it is suggested that the hypothalamus may play an important role in the pathogenesis of acromegaly in these cases.     

Persistent Phenothiazine Dyskinesia Treated with Tetrabenazine

Six patients with persistent phenothiazine dyskinesia were treated in a double-blind controlled trial with tetrabenazine 100 mg in divided dosage. In three patients the abnormal movements were abolished and in two others there was some improvement, but this was no greater than that achieved with the diazepam control. Tetrabenazine may be useful in the treatment of some patients with persistent phenothiazine dyskinesia.     

Possible Mechanisms of Neurodegeneration in Schizophrenia

Brain morphological alterations in schizophrenic patients have led to the neurodevelopmental hypothesis of schizophrenia. On the other hand, a progressive neurodegenerative process has also been suggested and some follow-up studies have shown progressive morphological changes in schizophrenic patients. Several neurotransmitter systems have been suggested to be involved in this disorder and some of them could lead to neuronal death under certain conditions. This review discusses some of the biochemical pathways that could lead to neurodegeneration in schizophrenia showing that neuronal death may have a role in the etiology or natural course of this disorder.     

A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response

In a significant proportion of melanoma patients, CTL specific for the melan-A(26/7-35) epitope can be detected in peripheral blood using HLA-A2/peptide tetramers. However, the functional capacity of these CTL has been controversial, since although they prove to be effective killers after in vitro expansion, in some patients they have blunted activation responses ex vivo. We used phenotypic markers to characterize melan-A tetramer(+) cells in both normal individuals and melanoma patients, and correlated these markers with ex vivo assays of CTL function. Melanoma patients with detectable melan-A tetramer(+) cells in peripheral blood fell into two groups. Seven of thirteen patients had a CCR7(+) CD45R0(-) CD45RA(+) phenotype, the same as that found in some healthy controls, and this phenotype was associated with a lack of response to melan-A peptide ex vivo. In the remaining six patients, melan-A tetramer(+) cells were shifted toward a CCR7(-) CD45R0(+) CD45RA(-) phenotype, and responses to melan-A peptide could be readily demonstrated ex vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells were examined, a similar dichotomy emerged. These findings demonstrate that activation of melan-A-specific CTL occurs in only some patients with malignant melanoma, and that only patients with such active immune responses are capable of responding to Ag in ex vivo assays.     

Identification of anti-plasmin antibodies in the antiphospholipid syndrome that inhibit degradation of fibrin

The combined presence of anti-phospholipid Ab (aPL) and thrombosis is recognized as the antiphospholipid syndrome (APS). The aPL represent a heterogeneous group of Ab that recognize various phospholipids (PL), PL-binding plasma proteins, and/or PL-protein complexes. Recently, we found the presence of antithrombin Ab in some APS patients and that some of these anti-thrombin Ab could inhibit thrombin inactivation by antithrombin. Considering that thrombin is homologous to plasmin, which dissolves fibrin, we hypothesize that some APS patients may have Ab that react with plasmin, and that some anti-plasmin Ab may interfere with the plasmin-mediated lysis of fibrin clots. To test this hypothesis, we searched for anti-plasmin Ab in APS patients and then studied those found for their effects on the fibrinolytic pathway. The results revealed that seven of 25 (28%) APS patients have IgG anti-plasmin Ab (using the mean OD plus 3 SD of 20 normal controls as the cutoff) and that six of six patient-derived IgG anti-thrombin mAb bind to plasmin with relative K(d) values ranging from 5.6 x 10(-8) to 1 x 10(-6) M. These K(d) values probably represent affinities in the higher ranges known for human IgG autoantibodies against protein autoantigens. Of these mAb, one could reduce the plasmin-mediated lysis of fibrin clots. These findings suggest that plasmin may be an important driving Ag for some aPL B cells in APS patients, and that the induced anti-plasmin Ab may act either directly, by binding to plasmin and inhibiting its fibrinolytic activity, or indirectly, by cross-reacting with other homologous proteins in the coagulation cascade to promote thrombosis.     

Outcome of Investigation of Patients with Presenile Dementia

Of 106 patients admitted for investigation to a neurological hospital with a presumptive diagnosis of dementia, 84 were confirmed to have intellectual impairment or loss of learning and memory function or both. A possible aetiology for the dementia was found in 36 of these 84 patients; the commonest causes discovered were intracranial mass lesions, arterial disease, and alcoholism. Fifteen of the 106 patients were found not to be demented but to have some other illness, most commonly depression. Of the whole series some 15% of the patients suffered from conditions that were amenable to treatment.     

The influence of cytostatic treatment on the initiation of plasma coagulation in patients with neoplastic diseases

The above described changes in the haemostatic system in acute leukemias are well known and underlined by many authors [1, 5, 6, 9]. It should be stressed that the results of particular nonspecific hemostatic tests in some patients may be within the normal range in spite of significant alterations in the activity of some blood coagulation factors and the presence of hemorrhagic symptoms. In the observations of some authors the factor VIII level is distinctly increased in the majority of acute leukemic cases, whereas the vitamin K-dependent blood coagulation factors show a low activity in some patients [6, 9]. It is not easy to interpret the different behaviour of the factor XI and XII level especially before antileukemic treatment. In 3/4 of all studied cases the factor XI activity was low, whereas the factor XII level was high in 1/4 of patients above the normal range. It may be that there is a specific inhibitor against the factor XI that is produced in acute leukemia. It must be stressed that the level of factor XI shows normal values during hematological remission.     

流行性出血热患者皮肤组织内病毒抗原及免疫复合物检测与意义

应用常规病理、免疫病理及超微病理技术,对３３例流行性出血热（ＥＨＦ）患者皮肤活检标本的病理变化及病毒抗原、免疫复合物进行观察,同时与血清病毒抗原、抗体及循环免疫复合物检出情况进行比较。在２３例ＥＨＦ患者皮肤微血管内皮细胞中检出病毒抗原,部分组织中可同时检出免疫球蛋白及Ｃ３,少数组织仅能检出病毒抗原或免疫球蛋白。配对血清小也可检出ＥＨＦ病毒抗原、抗体及循环免疫复合物。组织及血清免疫复合物形成与血清补体Ｃ３水平下降有关,组织内肥大细胞脱颗粒与血清ＩｇＥ水平升高相关,提示多种变态反应参与了流行性出血热的发病机制。     

Open rhinoplasty without skin-columella incision

For the last 4 years, the author has been using the open lower cartilaginous vault rhinoplasty, making an external cutaneous incision on the columella. After observing the improved results in patients with nasal tip, lateral crura, and medial crura difficulties, the author widely recommends the use of this procedure in selected patients. In addition to multiple advantages which have been reported useful in open-tip rhinoplasty in the past, the author has contributed two additional advantages: that it avoids scarring columella skin and that it can be extended to cope with defects of the entire lower cartilaginous vault. Disadvantages are some residual edema in some patients over a 6-months period and prolongation of operating time.     

What lies beyond the pain? A case report

The majority of people have back pain at some point in their lives and most are cured without any intervention. However, some patients develop chronic back pain and persistent disability. There is strong evidence that psychological factors significantly correlate with the development of chronic back pain. Back pain has also emerged as the strongest predictor of major depression. Assessing and treating patients in a manner that integrates psychosocial and biological aspects of care is the essence of excellent family medicine. This case illustrates the importance for primary care physicians of screening for depression and other psychosocial factors in assessing patients with persistent back pain.     

The Doctor-Patient Relationship: A Survey of Attitudes and Practices of Doctors in Singapore

This article reports the results of a survey, by mailed questionnaire, of the attitudes, values and practices of doctors in Singapore with respect to the doctor-patient relationship. Questionnaires were sent to a random sample of 475 doctors (261 general practitioners and 214 medical specialists), out of which 249 (52.4%) valid responses were completed and returned. The survey is the first of its kind in Singapore. Questions were framed around issues of medical paternalism, consent and patient autonomy. As the doctors were exposed to Western ethical concepts in their training, we were not surprised to find that they would mostly allow patients some say in decision-making and keep patients reasonably informed. In respecting patient autonomy, they would usually seek to influence patient choice by persuasion. However, the residual 'Asian-ness' of doctors in Singapore gives rise to some inconsistencies between values and practices. Many doctors still believe that a number of their patients are incapable of rational choice. There is some lack of openness in telling patients the whole truth. When patients choose to refuse treatment, many doctors are prepared to involve family members in making a consensus decision.
Doctors were also asked how they made ethical judgements in the face of dilemmas, and how they would like disputes with patients to be resolved. By and large, the doctors prefer to make their own judgements rather than to rely on rules. They also wish to keep the law courts out of disputes with patients, preferring less public ways of settling disputes.     

The throat flora and its mitogenic activity in patients with Kawasaki disease

The etiology of Kawasaki disease (KD) remains unknown, although some infectious organism has been suggested as the cause. Recent studies suggest that some bacterial toxins with superantigen activity are involved in its pathogenesis, but no specific bacterial toxin has yet been identified. Throat swabs for bacterial culture were obtained from 21 patients with KD and 20 with other febrile illnesses as controls. Mitogenic activity in culture supernatants obtained from individual bacterial strains was measured by lymphocyte proliferation assay. Sixty-one bacterial strains were isolated from KD patients, and 62 strains from control patients. There was no apparent difference in bacterial species in the throat flora between KD patients and febrile controls. Moreover, total and individual mitogenic activity of strains from KD patients was no greater than that of strains from febrile controls. The bacterial superantigen activity of throat flora may not play a major role in the pathogenesis of KD.     

Abnormal methylation does not prevent X inactivation in ICF patients.

DNA undermethylation is a characteristic feature of ICF syndrome and has been implicated in the formation of the juxtacentromeric chromosomal abnormalities of this rare syndrome. We have previously shown that in female ICF patients the inactive X chromosome (Xi) is also undermethylated. This result was unexpected since female ICF patients are not more severely affected than male patients. Here we show that CpG island methylation is abnormal in some ICF patients but in other ICF patients, the difference in methylation pattern between Xi and Xa (active X) is maintained. The consequences of Xi undermethylation on gene expression were investigated by enzyme assays. They showed that significant gene expression did not correlate with CpG island methylation status. The widespread Xi undermethylation does not affect overall Xi replication timing and does not prevent Barr body formation suggesting that a normal methylation pattern is not required for normal chromatin organization of Xi. Molecular investigation of some X-chromosome intron regions showed that the methylation changes in ICF female patients extend to non CpG islands sequences. Our results suggest that the genetic alteration of DNA methylation in ICF syndrome has little consequence on X chromosome gene expression and chromatin organization.     

Possible mechanisms of anosognosia: a defect in self-awareness.

Anosognosia of hemiplegia is of interest for both pragmatic and theoretical reasons. We discuss several neuropsychological theories that have been proposed to explain this deficit. Although for psychological reasons people might deny deficits, the denial hypothesis cannot account for the hemispheric asymmetries associated with this disorder and cannot explain why some patients might deny one deficit and recognize another equally disabling deficit. There is some evidence that faulty feedback from sensory deficits, spatial neglect and asomatognosia might be responsible for anosognosia in some patients. However, these feedback hypotheses cannot account for anosognosia in all patients. Although the hemispheric disconnection hypothesis is appealing, disconnection is probably only a rare cause of this disorder. The feedforward intentional theory of anosognosia suggests that the discovery of weakness is dependent on attempted action and some patients might have anosognosia because they do not attempt to move. We present evidence that supports this theory. The presence of one mechanism of anosognosia, however, does not preclude the possibility that other mechanisms might also be working to produce this disorder. Although a large population study needs to be performed, we suspect that anosognosia might be caused by several of the mechanisms that we have discussed. On the basis of the studies of impaired corporeal self-awareness that we have reviewed, we can infer that normal self-awareness is dependent on several parallel processes. One must have sensory feedback and the ability to attend to both one''s body and the space where parts of the body may be positioned or acting. One must develop a representation of the body, and this representation must be continuously modified by expectations (feedforward) and knowledge of results (feedback).     

Fracture rates in patients with growth hormone deficiency

There is some evidence that bone mass is reduced in the majority of adult patients with growth hormone deficiency (GHD), suggesting that such patients have an increased risk of fractures and clinically significant osteoporosis. To date, there have been only two reports of fracture rates in patients with hypopituitarism. Both these retrospective studies show an increased fracture prevalence in this patient group compared with the general population, but patient numbers were low for assessing fracture rates. However, an analysis of data from a large-scale pharmacoepidemiological survey of adults with GHD, KIMS (Pharmacia International Metabolic Database), confirms the findings of these earlier studies. The prevalence of all fractures among patients in KIMS was 2.7 times that in the control population, and the risk of fracture was independent of whether patients had isolated GHD or multiple pituitary hormone deficiencies. The results suggest that GHD is a risk factor for fractures, if a direct endocrine cause is assumed. Notably, there are some data on subgroup analyses from KIMS suggesting that growth hormone replacement therapy may help to reduce fracture risk, although further evidence is needed to confirm this effect.     

Emergency Resection in Treatment of Diverticular Disease of Colon Complicated by Peritonitis

Of a consecutive series of 25 patients with peritonitis secondary to colonic diverticular disease all, except one with faecal peritonitis, underwent some form of emergency resection.All the three patients with faecal peritonitis died, but the 22 with purulent peritonitis survived. The average duration of the emergency admission of the 22 survivors was 25.4 days, and in nine (41%) of them intestinal continuity had been restored by the end of that admission.Thus some form of emergency resection is the operation of choice in patients with spreading peritonitis due to diverticular disease of the sigmoid colon.     

Therapeutic Agents in Acne Vulgaris: I. Tetracycline

A total of 120 consecutive patients with pustular and cystic acne vulgaris were selected for study. Patients were assigned a placebo and a tetracycline medication in a random method. Of the 53 patients who were given tetracycline, 45 showed some response, which was fair in 19 and excellent in 26. Of the 55 patients who received placebo, 24 showed no response while 31 showed some improvement. No side effects were reported. The difference in response between the two groups is statistically significant. It is concluded that administration of 250 mg. tetracycline four times daily, even for periods as short as two weeks, enhances the likelihood of improvement of cystic or pustular acne vulgaris.     

CORTICOTROPIN (ACTH) AND CORTISONE—Newer Concepts of Their Use in Clinical Practice

On the basis of three years'' experience with corticotropin and cortisone, it seems probable that the place of these hormones in clinical medicine will be one of increasing importance. At present they may be used to attain certain specific objectives:1. To return a large number of chronic invalids to a place of full activity in the community. This applies particularly to patients with rheumatoid arthritis and bronchial asthma. Many years of continuous therapy will be required in the majority of such patients.2. As life-saving agents in patients with certain diseases of unknown etiologic delineation that almost always cause death. In some patients treated for some of those diseases, therapy may eventually be discontinued.3. As life-saving agents (in conjunction with intensive antibiotic therapy) in patients with severe infections inadequately responsive to chemotherapy alone.Many of the untoward effects of hormonal therapy may be minimized or prevented by appropriate adjuvant measures.     

Corticotropin (ACTH) and cortisone; newer concepts of their use in clinical practice

On the basis of three years' experience with corticotropin and cortisone, it seems probable that the place of these hormones in clinical medicine will be one of increasing importance. At present they may be used to attain certain specific objectives:1. To return a large number of chronic invalids to a place of full activity in the community. This applies particularly to patients with rheumatoid arthritis and bronchial asthma. Many years of continuous therapy will be required in the majority of such patients.2. As life-saving agents in patients with certain diseases of unknown etiologic delineation that almost always cause death. In some patients treated for some of those diseases, therapy may eventually be discontinued.3. As life-saving agents (in conjunction with intensive antibiotic therapy) in patients with severe infections inadequately responsive to chemotherapy alone. Many of the untoward effects of hormonal therapy may be minimized or prevented by appropriate adjuvant measures.     

Benign familial tremor treated with primidone.

Primidone given to a patient for epilepsy produced an unexpected reduction in benign familial tremor. Over the next eight years the drug was therefore tried in a prospective study of 20 other patients with benign familial tremor alone. Of these, six could not tolerate the drug because of vertigo and nausea but 12 obtained a good response, which in some cases was dramatic. Investigations in two patients suggested that the effect was mediated predominantly by derived phenylethylmalonamide, though primidone had some effect, since tremor recurred slightly on withdrawing the drug despite a constant or rising blood phenylethylmalonamide concentration. Primidone is highly effective in benign familial tremor. More patients with the condition are intolerant of the drug than are usually found with epilepsy.