Primary hyperparathyroidism. Pathogenesis--diagnosis--therapy]

A report is given on 33 patients with primary hyperparathyroidism who underwent surgical treatment in our institution in the period from 1980 to 1989. In 57 per cent of the cases a hypercalcaemic syndrome was present. The primary hyperparathyroidism manifested itself in 75 per cent at the kidneys in the form of nephrolithiasis. One third of the patients showed a renal manifestation form exclusively. Remarkable is the relatively high number of exclusively gastrointestinal manifestations (11 per cent). In all patients the diagnosis was established on the coincidence of hypercalcaemia and increased parathormone in the serum. Preoperative localization diagnostics by means of parathyroid sonography, computed tomography and scintigraphy yielded unsatisfactory results. A satisfactory accuracy with regard to the lateral localization of the hyperfunctioning parathyroid tissue can presently be achieved only by selective catheterization of the cervical vein with determination of the parathormone. 35 patients clinically suspected of having primary hyperparathyroidism were subjected to a total of 44 operative interventions, i.e., apart from 35 primary operations, 7 secondary and 2 tertiary interventions. Of the 35 primary operations, 10 (28.6 per cent) were without success. This was due to 2 misdiagnoses and 8 cases with insufficient intraoperative exploration and premature discontinuation of the operation. In 67 per cent of the cases, there was a predominance of the solitary parathyroid adenoma, which was chiefly located at the dorsal lower thyroid poles. In order to reduce the number of unsuccessful primary interventions, a surgically-tactical approach is recommended.     

Lethal enhancement of therapeutic doses of acetaminophen by alcohol

Summary A 47-year-old man undergoing supervised alcohol detoxification developed severe liver disease after receiving small doses of acetaminophen. Autopsy revealed extensive hepatic necrosis. Proposed mechanisms for alcohol potentiation of acetaminophen hepatotoxicity are described. We feel acetaminophen should not be routinely used for patients with active alcoholism unless its safety can be established.     

Human mini-chromosomes in mouse embryonal stem cells

We have introduced human mini-chromosomes of 4 Mb and approximately 15 Mb in size into mouse embryonal stem cells. Although these human mini- chromosomes are stable in hamster and chicken cells, they re-arrange or segregate aberrantly in the embryonal stem cells and are rapidly lost in the absence of selection. However, one of the mini-chromosomes re- arranged, acquired mouse centromeric sequences and was then stably maintained for at least 60 population doublings in culture. This mini- chromosome, which is 4 Mb in size, is a candidate for a mouse germ line chromosome vector.      

The source of 'paradoxical lateralization' of cortical evoked potentials to posterior tibial nerve stimulation

We report the potentials elicited by posterior tibial nerve stimulation and recorded simultaneously from the scalp and from electrodes within the interhemispheric fissure. The primary cortical potential was recorded from cortex contralateral but from scalp ipsilateral to the stimulated nerve. The scalp recordings thus demonstrated "paradoxical lateralization" as reported previously, and the similar morphology of the scalp and contralateral cortical recordings confirm that this "paradoxical lateralization" is most likely the result of a horizontal dipole located within the interhemispheric fissure.     

A continuing controversy: magnesium sulfate in the treatment of eclamptic seizures

It would appear from the above that Pritchard agrees with the use of some agents other than magnesium sulfate that have known anticonvulsant properties. We believe that the subject at issue is whether magnesium sulfate should be used in treating the seizures of eclampsia. In our "Controversies" article, we do not address the issue of whether magnesium sulfate modifies pathophysiological factors leading to preeclampsia, but restrict ourselves to the treatment of the seizure per se, once seizures supervene, and the avoidance of their recurrence. The pathophysiological mechanisms and optimal treatment of preeclampsia and of eclampsia (excepting seizures) remain to be determined, as does the use of magnesium sulfate in this condition. Eclamptic seizures are clinically and electroencephalographically indistinguishable from generalized tonic-clonic seizures. Whether seizures arise in or out of the setting of preeclampsia, they should be treated as are other seizures, with known anticonvulsants. Controlled clinical trials are needed to address the effectiveness of alternative antiseizure regimens.     

Unfinished feticide: the ethical problems

Dr. Jansen's paper raises three main issues. The one with which he himself is most concerned is the question of which methods of abortion are ethically right, and whether methods which risk the birth of a damaged baby are wrong. But there are two others: first, how the (originally unintended) birth of a live but damaged child alters the moral situation, and secondly, whether the overcoming of sterility by inducing a multiple pregnancy in which some of the fetuses have to be killed in order for any of them to survive is at all morally acceptable.     

Induction of electrical excitability by NGF requires autocrine action of a CNTF-like factor

The overlapping expression of neurotrophin and neural cytokine receptors indicates that most neuronal populations are responsive to both classes of factors, yet relatively little is known about how these two trophic signaling systems interact to regulate neuronal phenotype. We report here that one hallmark of NGF's effects on target cells, the induction of membrane electrical excitability, requires the intermediary action of a CNTF-like factor. We found that NGF's regulation of voltage-gated potassium channels, unlike its regulation of voltage-gated sodium and calcium channels, involves a CNTF-like autocrine/paracrine loop. We showed that NGF induces secretion of a soluble factor that mimics the action of exogenous CNTF in regulating voltage-gated potassium channels and that NGF's ability to regulate this potassium channel is blocked by three independent reagents that inhibit the signaling of CNTF and/or related factors. The identity of this autocrine factor does not appear to be CNTF itself. Thus, a CNTF-like autocrine/paracrine factor is both necessary and sufficient for the regulation of potassium channels by NGF and is a key determinant of the type of electrical excitability that NGF induces in target cells.     

单克隆抗体博来霉素A6偶联物对白血病细胞特异性结合与内化

抗CCT2单克隆抗体博来霉素A6偶联物可吸附胶体金颗粒(McAb-A6-Au)。电镜观察表明,在4℃,1h,表面有McAb-A6-Au颗粒的CEM细胞最高达78%;在37℃,4h,内化McAb-A6-Au颗粒的CEM细胞高达72%。而抗原性无关的U937细胞仅为14%。并且McAb-A6-Au颗粒能直接穿过细胞膜、核膜进入细胞浆和细胞核。37℃,1h已有10～18%的CEM细胞核内有McAb-A 6-Au颗粒。实验结果提示了单抗与博来霉素A6的偶联物与选择性地结合靶细胞,而且进入细胞速度快、穿透力强,有可能成为治疗白血病药物。