StMichael 写了： 2023年 12月 30日 16:42 又去仔细读了一下这篇文章，发现里面一个discrepancy
贴了一部分原文如下；
关键信息有几点：
1. 朱令1994年底全部头发脱落(bald);
2. ZL1995H9 这根7厘米头发最晚脱落时间是1994年底。作者原文是“The victim went home in mid-December and became
completely bald in late December 1994, a period of 2 weeks during which hair ZL1995H9 likely fell off.”
3. ZL1995H9 从发尖到发根生长时间根据亚洲女性平均头发生长速度，被作者估算生长时间171天
4. 这根头发上，第一个高于背景的铊峰出现在第17天。到头发脱落153天。
5. 八月一日到十二月底=153天，这样计算，第一个铊峰出现，最晚时间在八月一日前后
但是作者在另一个图里，把这个峰画在了八月中旬以后。
下面来自wikipedia:
https://zh.wikipedia.org/zh-hans/%E6%9C ... B%E4%BB%B6
据其同学提供的信息，1994年10月，朱令的眼睛曾两次发生暂时性失明以及数日的视力模糊，虽然她先后分别在清华大学校医院以及清华大学指定的北医三院接受眼科检查，但医院并没有检查出病因[14]。
从1994年11月24日起，朱令开始出现奇怪的中毒症状：起先是肚子疼，吃不下饭；接着（12月5日）胃部不舒服；最后（12月8日）她的头发开始脱落，并在几天内掉光。1994年12月11日晚上，朱令带病坚持参加清华民乐队在北京文艺厅专场演出，朱令表演古琴独奏《广陵散》[15]。12月23日，朱令入住北京市同仁医院消化内科病房，检查尿砷尿汞均正常[16]，影像学检查和内分泌各项检查正常[17]。但是，甲皱处呈严重微循环异常状态[17]。住院期间，辅以营养支持和中医治疗，朱令的病情得到缓解，并长出头发[17]。虽然没有查出病因，朱令在住院一个月以后，于1995年1月23日出院[17]。
4.3
Pre- and post-poisoning basal levels for thallium and lead
The victim’s hair heavy metal levels prior to the poisoning period (1994–1995) was established by analyzing the longest hair, ZL1995H1 (∼30 cm), which should have fallen from the victim in 1994, since she became completely bald at the end of that year and never grew hair of such length in 1995. Thallium and lead concentrations of the first ∼3 cm from the hair root of this hair were 2.8 ng g −1 and 1.4 μg g −1 , respectively, close to the levels (3.7 ng g −1 and 0.8 μg g −1 , respectively) detected near the root of a hair collected in 2015 (ZL2015H100). Analysis of another very long hair, ZL1995H2 (∼26 cm), also showed very similar levels of thallium and lead, respectively ( Table 2 ).
Table 2
Averaged Tl and Pb concentrations in each analyzed hair samples. For comparison purpose, only the contents in the last ∼3 cm hair shaft near the root of long hair samples (>3 cm) were averaged. For short hair samples (<3 cm), the contents of the entire length were averaged.
Sample ID Collecting time Total length (cm) Tl (ng g −1 ) Pb (μg g −1 )
ZL2015H100 2015 ∼10 3.7 0.8
ZL1995H1 1995 ∼30 2.8 1.4
ZL1995H2 1995 ∼26 2.8 0.6
ZL1995H3 1995 ∼1 165 12
ZL1995H5 1995 ∼0.7 182 43
ZL1995H8 1995 ∼4 15 4
ZL1995H9 1995 ∼7 40 2
4.4
Longitudinal distribution of thallium in Hair ZL1995H9
The entire length of a ∼7 cm long hair (ZL1995H9) was scanned from the tip to the root. The longitudinal distribution profile of thallium was shown by the concentration plotted against the distance from the hair tip and the converted hair growth time, which was estimated based on the mean Asian hair growth rate of 411 (±53) μm/day
. Approximately 25 distinguishable peaks, with maximum peak concentrations at or above 50 ng g −1 (∼20-fold above the basal level), were resolved along the entire hair shaft ( Fig. 2 A). The intervals between the sharp maxima of the thallium signal peaks varied between 0.5 and 8.6 mm, corresponding to ∼2–20 days. The distance between the first and the last recognizable thallium peak was ∼55 mm, corresponding to at least ∼4 months of hair growth time. An exceptionally tall peak of ∼530 ng g −1 in the middle of this hair shaft indicated a single exposure to an unusually large dose (∼200-fold above the basal level) of thallium. The duration of each peak was ∼2 days, in agreement with the previously observed rapid clearance of thallium from blood
. The thallium concentration baseline escalated near the hair root and was juxtaposed with a cluster of peaks with maximum concentrations of ∼150–220 ng g −1 , suggesting the victim had more frequent exposure to increased doses of thallium (50–80-fold above the basal level) ∼3 weeks before this hair fell out.
Fig. 2
(A) The longitudinal Tl profile in Hair ZL1995H9 represented by its concentration against the distance from the hair tip (bottom X axis) and the converted hair growth time (top axis). (B) Alignment of the Tl profiles detected in the 1st and 2nd scan of ZL1995H9.
A repeated scan of the entire length of this hair showed identical 205 Tl distribution profile, but at a slightly higher level ( Fig. 2 B), confirming that the thallium had been absorbed internally and incorporated during the formation of the hair shaft via diffusion from blood to the actively growing follicle. This result was in agreement with the conclusion from the previous analysis of the victim’s blood and urine at the time of the diagnosis
.
4.5
Longitudinal distribution of thallium in Hair ZL1995H5
In contrast to the smooth surface appearance of hair ZL1995H1, ZL1995H2 and ZL1995H9, a rugged surface and dark gray lateral stripes were observed under the microscope ( Fig. 3 ), on a very short hair, ZL1995H5 (∼0.7 cm). Numerous congested thallium peaks spreading along the entire length of this hair were revealed by the first LA-ICP-MS scan, with concentrations varying between 150–500 ng g −1 (∼50–180 fold above the basal level). Intervals between the sharp maxima of most of the thallium signal peaks were ∼0.1–0.3 mm which corresponded to ∼6–18 h, suggesting consistent daily intakes of thallium. Surprisingly, significantly increased signals of lead ( 206 Pb, 207 Pb and 208 Pb) were also observed in this hair, with several large 208 Pb peaks aligning well with thallium peaks ( Fig. 4 A). The highest 208 Pb peak was ∼100-fold above the Pb baseline detected in ZL1995H1.
Fig. 3
Microscopic pictures of hair samples. Before laser ablation, ZL1995H2 (A). After laser ablation ZL1995H2 (B), ZL1995H9 (C), ZL1995H5 (D). The red arrow indicated the laser ablated lines. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
(A) Longitudinal distribution of Tl and Pb over the entire length of ZL1995H5, (B) alignment of the Tl profiles from the 1st and 2nd scan of ZL1995H5, (C) alignment of the Pb profiles from the 1st and 2nd scan of ZL1995H5.
The second scan of this hair revealed a similar, but not exactly overlapping, Tl profile ( Fig. 4 B), again slightly higher than the level detected in the first analyses. The misalignment of 205 Tl peaks between the two scans likely resulted from the damaged hair surface structure and disorganized cuticle, which had been observed before on the hair shaft from a victim who died of severe thallium poisoning
. In addition, the lead concentration decreased by ∼3-fold, but still ∼10-fold above the basal level ( Fig. 4 C), likely due to the complex reasons discussed below. Nevertheless, with much more frequent and higher thallium peaks and the co-appearance of large amount of lead, Hair ZL1995H5 apparently represented an acute poisoning stage distinguishable from the mainly chronical exposure episode represented by Hair ZL1995H9. Analysis of additional hairs revealed thallium and lead distribution profiles either very similar to ZL1995H9 or similar to ZL1995H5. The averaged concentrations for both metals near the hair root in each analyzed hair sample were shown in Table 2 .
Previous studies on the distribution of trace elements in human hair have found that lead and iron appeared to be accumulated near the periphery of the hair regardless of endogenous incorporation or external deposit, presumably due to the preferred binding of these metals by components in the hair cuticle and/or the alternative incorporation route of endogenous elements into hair shaft via secretion from the sebaceous glands after the formation of the hair shaft
. We speculated that the significant amount of lead detected in the outer layers of hair ZL1995H5 should not be exclusively ascribed to contamination for at least three reasons. First, the absence of such elevated level of lead in the surface of longer hairs (ZL1995H1, ZL2991H2, ZL1995H9) suggest that the victim was not exposed to an unusual level of environmental lead either in school or at home during this period. Second, it was unlikely that this batch of hair samples have been contaminated by environmental lead during the storage or in the process of our analysis, since higher level of lead was only detected in the very short hairs. Third, exogenously deposited lead would unlikely produce peaks that were correlated with the internally ingested thallium. Nevertheless, an unambiguous determination on whether the victim had ingested large dose of lead during the second thallium poisoning period would require analysis of additional biological specimens that were collected right after the assumed poisoning period.
4.6
Alignment of thallium and lead distribution profiles with the victim’s symptoms
The victim had experienced alopecia twice: loss of her long hair at the end of 1994, and then loss of all newly grown short hair in March 1995. Based on the hair length, ZL1995H9 likely fell from the victim during the first occurrence of alopecia, and ZL1995H5 likely fell during the second occurrence. Fig. 5 showed the alignment of the thallium and lead distribution profiles in these two hairs with the victim’s symptoms and life track from late 1994 to early 1995.
Fig. 5
Alignment of the Tl and Pb distribution profiles in ZL1995H9 and ZL1995H5 with the victim’s symptoms and life track during 1994–1995.
The toxicity of thallium stems from its ability to replace potassium and interfere with various potassium-dependent physiological processes due to similar charge and ionic radius. Thallium ions can be absorbed by human body rapidly and almost completely via virtually any route (ingestion, inhalation, skin contact), causing a wide spectrum of symptoms including gastroenteritis, multi-organ failure and neurologic injuries. The onset of poisoning signs and symptoms varies depending on both dose and exposure route
. Alignment of ZL1995H9 with the first episode indicated that the victim had already been exposed to thallium for ∼3 months before the abrupt start of the striking poisoning symptoms. The sporadic intakes of relatively small doses during this prolonged period did not cause any apparent health problems, except a sudden and temporary vision loss occurring sometime in the fall of 1994. This may be attributed to the single high dose of thallium detected in the middle of ZL1995H9. The lack of any gastrointestinal or neurological response upon such a large exposure may suggest that thallium was possibly absorbed through eye contact, which usually only resulted in local irritation instead of systematic effects . It is also noteworthy that the victim used to wear contact lens but had to switch to glasses after this incident. The more frequent and larger thallium peaks near the root of ZL1995H9 correlate with the appearance of the hallmark signs of systematic thallium intoxication starting from early December 1994, including gastrointestinal manifestations (stomach pain, nausea and vomiting) that are characteristics of oral ingestion of thallium, ascending peripheral neuropathy (pins and needles sensation in the hands and feet), and gradual hair loss. Such correlation may indicate a change in exposure route to oral ingestion along with the transition from the chronic to acute poisoning. The victim went home in mid-December and became completely bald in late December 1994, a period of ∼2 weeks during which hair ZL1995H9 likely fell off. After a short remission with hair re-growing, the victim returned to school in late February 1995, only soon suffered another round of acute symptoms that ultimately forced her to go back to home again in early March. She then lost all the newly grown short hair. ZL1995H5 likely fell off during this period, and the short, yet consistent, exposure to the large amount of thallium reflected by this hair shaft would account for these acute intoxication manifestations as well as the clinical signs documented after she was sent to the hospital, including delirium, seizure, convulsion and eventually slipping into a coma for several months. More than a month later, quantitative GF-AAS analysis (measuring only thallium) was conducted and revealed significant amounts of thallium in her urine, blood, cerebrospinal fluid, hair and nails . Continuing monitor of the thallium levels in the victim’s blood and urine during the following medical treatment with thallium-specific antidotes demonstrated the gradual elimination of thallium from her body. The victim was eventually brought back to consciousness ∼4 months later, but suffered permanent memory impairment, another neuropsychological effect which can be caused by thallium intoxication . Computed tomography (CT) scan of her brain revealed both cerebral and cerebellar atrophy
.
Interestingly, lead could also attack both central and peripheral nervous system and, in the situation of acute exposure of large doses, trigger a set of polyneuropathy clinical signs that are very similar to those resulting from thallium poisoning, including severe pain, muscle weakness, delirium, convulsion and coma. An important mechanism of lead toxicity arises from its ability to replace divalent cations that are necessary for some critical cellular activities. For example, lead can replace calcium ions and pass through the blood-brain barrier, causing neurological abnormalities including memory-related neurotransmitter activities that may lead to memory loss
. Therefore, the possible co-ingestion of lead with thallium in the second poisoning episode, as indicated by the co-presence of large amount of thallium and lead in ZL1995H5, would also synchronize with the victim’s symptoms during that period. However, alopecia was a distinct symptom only associated with thallium poisoning , thus the original diagnosis, medical treatment and forensic investigation have only focused on thallium. Thallium is also more acutely toxic than lead
, which explains why the victim responded appreciably well to the thallium-specific antidotes, even though more lead than thallium was detected in ZL1995H5. Prior to this work, there had been no suspicion that the victim might have been co-poisoned by another heavy metal, since the amount of thallium detected in her body could adequately explain all the observed symptoms and responses following the medical treatment. This case thus highlighted the importance of assessing multiple elements in different biological specimens to aid in the medico-legal investigation of suspicious heavy metal poisoning upon clinical observations.
5
Conclusions
Based primarily on the LA-ICP-MS analysis of two hairs, we have reconstructed the poisoning chronology of an unsolved cold case, which correlated well with the victim’s original symptoms. The results have also exposed a previously unknown chronic poisoning period with sporadic thallium exposures, the potential involvement of another heavy metal (lead), and clues on the possible routes of exposure at different poisoning stages. Future work may include analyzing additional hairs to investigate whether the first thallium peak detected in ZL1995H9 indeed represents the beginning of the first poisoning period. The analysis of other biological specimens collected from the victim around the poisoning period could be carried out to verify whether she had indeed co-ingested lead with thallium during the second poisoning period. Nevertheless, our work has demonstrated the capability of using single hair LA-ICP-MS analysis to retrieve information from meager specimens for the reconstitution of a prolonged and complicated heavy metal poisoning case. We hope this work could also raise the awareness of the importance of assessing multiple elements in different bio specimens due to the overlapping symptoms caused by some heavy metals and the intrinsic limitation of hair analysis to distinguish the internal versus external origins of certain elements. One of the strengths of ICP-MS analysis is the rapid determination of low levels of multiple elements simultaneously. The simple LA-ICP-MS analytical procedure developed in our work could be of considerable medical and forensic importance to resolve complicated heavy metal poisoning incidents. Careful collection and curation of hair samples from poisoning victims would also aid in the establishment of a precise time-line for the ingestions of the heavy metals.
Authors’ contributions
RDA conducted the LA-ICP-MS experiments and the data analysis, and contributed to the manuscript writing; MH conceived this project, conducted the data analysis and interpretation, and wrote the manuscript.
非常有道理。
