Biomedical subjects

A Kawata

Publications and source records attributed to A Kawata.

At least 19 recordsLinked to original sources

PubMed1997

Prominent sensory and autonomic disturbances in familial amyotrophic lateral sclerosis with a Gly93Ser mutation in the SOD1 gene.

A missense mutation (Gly93-->Ser) was identified in exon 4 of the Cu/Zn superoxide dismutase (SOD1) gene of a 48-year-old Japanese man with familial amyotrophic lateral sclerosis (FALS). The SOD1 activities in the fibroblasts and in a lysate of erythrocytes of the patient did not differ from those of healthy controls. The clinical characteristics of the patient were fairly slow progression of the illness, prominent sensory impairment, urinary disturbance and blood pressure fluctuation due to sympathetic hyperactivity. The severe sensory and autonomic disturbances, association of which with FALS has not been previously reported, may represent specific clinical features associated with the Gly93Ser mutation or may indicate the variability of clinical findings even in patients with the same mutation.

Amyotrophic Lateral Sclerosis↗

PubMed1997

Development of a severe combined immunodeficiency (SCID) mouse model consisting of highly disseminated human B-cell leukemia/lymphoma, cure of the tumors by systemic administration of immunotoxin, and development/application of a clonotype-specific polymerase chain reaction-based assay.

A new severe combined immunodeficiency (SCID) mouse model consisting of highly disseminated human B-cell leukemia/lymphoma was developed by i.v. inoculation of BALL-1a, an in vivo adapted malignant B-cell line. A 100% transplantability was achieved in nonpreconditioned SCID mice using various BALL-1a doses between 2.5 x 10(4) and 6 x 10(6) cells. Hind-leg paralysis preceded the death of the mice. Utility of the developed tumor model for the therapeutic studies was investigated by i.v. administration of an anti-B-cell monoclonal antibody SN7 (IgG1) and its conjugate with deglycosylated ricin A chain (dgRA). The therapy was initiated 2, 4, or 6 days after tumor inoculation using 4 x 24 microg of SN7-dgRA or 4 x 20 microg of SN7; the total dose (96 microg) of SN7-dgRA corresponded to 14% of the LD50 dose. SN7-dgRA showed a strong antitumor efficacy in all groups of treated mice. All of the day-2 group mice (n = 7) and six (66.7%) of the day-4 group mice (n = 9) survived healthily for as long as followed (240 days), whereas four (57.1%) of the day-6 group mice (n = 7) survived healthily for as long as followed (200 days). Unconjugated SN7 showed a significant antitumor efficacy but was less effective than SN7-dgRA. A PCR-based assay specific for the clonogenic BALL-1a tumor was developed and applied to determine tumors in various organs of BALL-1a-bearing SCID mice. The assay was highly sensitive in screening for trace quantities of residual tumors in various organs of SCID mice, and it could detect 1 malignant cell/2.5 x 10(5) tissue cells. The PCR-based assay was shown to be much more powerful than the conventional histological analysis in detecting residual tumors. Furthermore, we could estimate quantities of the detected tumors by the PCR-based assay. It is remarkable to find that all examined organs of some of the SN7-dgRA-treated mice were tumor-free as determined by the clonotype-specific PCR-based assay. The present results show the usefulness of the newly developed SCID mouse model, SN7-dgRA, and the clonotype-specific PCR-based molecular assay for the study of therapy of human B-cell leukemia/lymphoma.

Animals↗

PubMed1997

Adult-onset type II citrullinemia: clinical pictures before and after liver transplantation.

In a 25-year-old man with adult-onset type II citrullinemia, liver transplantation resulted in elimination of hyperammonemia and amino acid abnormalities associated with the disease. Postoperatively, a high intensity area in the right cingulate gyrus on a T2-weighted brain magnetic resonance imaging (MRI) also disappeared, suggesting that it reflected an early reversible lesion due to the hyperammonemia. Moreover, the serum level of pancreatic secretory trypsin inhibitor (PSTI), which had been elevated, was normalized. Since the levels of PSTI mRNA and PSTI have been reported to be increased in the livers of type II citrullinemia patients, measurement of serum PSTI levels could aid in the diagnosis of this disease.

Adult↗

PubMed1996

Absence of SOD1 gene abnormalities in familial amyotrophic lateral sclerosis with posterior column involvement without Lewy-body-like hyaline inclusions.

A 65-year-old man with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement showed fairly slow progression of the illness and lived with the aid of a respirator for 12 years. Neuropathological examinations showed simultaneous involvement of the pyramidal tract and lower motor neurons as well as degeneration in the Clarke's nucleus- spinocerebellar tract-middle root zone of the posterior column, the pallidoluysian system, the medullary reticular formation, and widespread anterolateral columns of the spinal cord. However, the patient had no Lewy-body-like hyaline inclusions, which are characteristic features of this form of familial ALS. Moreover, no abnormalities were found in his SOD1 cDNA sequences. There seem to be certain heterogeneities in familial ALS with posterior column involvement, and SOD1 gene abnormalities may be involved in the pathomechanism in rapidly progressing ALS, in which there are Lewy-body-like hyaline inclusions.

Aged↗

PubMed1996

Receptor binding and antagonist properties of a novel endothelin receptor antagonist, TAK-044 [cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl) carbonyl]-L-alanyl-L-alpha-aspartyl-D-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl]disodium salt], in human endothelinA and endothelinB receptors.

Receptor binding and antagonist properties of an endothelin (ET) receptor antagonist, TAK-044 ¿cyclo[D-alpha-aspartyl-3-[(4-phenylpiperazin-1-yl) carbonyl]-L-alanyl-L-alpha-aspartylD-2-(2-thienyl) glycyl-L-leucyl-D-tryptophyl]disodium salt¿, were investigated using recombinant human ETA and ETB receptors expressed in Chinese hamster ovary cells. The membranous ETA receptor was shown to be heterogeneous in ET-3 binding affinity (Hill coefficient = 0.54, Kd1 = 390 pM and Kd2 = 8.1 nM). This heterogeneity disappeared upon the addition of guanosine-5'-O-3-thiotriphosphate (Hill coefficient = 0.95, Kd = 7.8 nM). The Kd (from a computer program LIGAND analysis) and Ki (from Dixon plot analysis) values of TAK-044 were 95 and 120 pM for the membranous ETA receptor and 41 and 60 nM for the ETB receptor, respectively. The Kd values of TAK-044 for the ETA receptor was comparable to that of ET-1. The Ki values of TAK-044 for the cellular ETA and ETB receptors were 130 pM and 130 nM at 5,000 cells/well and 1.3 and 590 nM at 50,000 cells/well, respectively. Dixon plot analysis indicated that TAK-044 is a competitive inhibitor of ET-1 binding. TAK-044 inhibited ET-1-induced phosphatidylinositol hydrolysis and arachidonic acid release at 50,000 cells/well in a competitive manner with respective pA2 values of 8.5 and 8.7 in the ETA-expressing cells and 7.4 and 6.6 in the ETB-expressing cells. TAK-044 suppressed ET-1-induced transient increase in intracellular Ca+2 concentration in the ETA- and ETB-expressing cells with respective IC50 values of 2.8 and 230 nM. TAK-044 is a potent and competitive ETA receptor antagonist which simultaneously exhibits definite antagonist activity at the ETB receptor.

Animals↗

PubMed1996

[Clinical and myopathological studies on rigid spine syndrome].

Rigid spine syndrome (RSS) is thought to be a group of heterogeneous muscle disorders. We reviewed the clinical and myopathologic findings of 55 patients with RSS including 49 previously reported and our own 6 patients. The results were as follows: the first, 80% showed restrictive ventilatory failure and 40% atrophy of the sternocleidomastoid muscle (SCM), which became manifest in the early stage of the illness, namely in less than 5 years from the onset. The second, paraspinal muscles usually began to be involved from the cervical semispinal muscle extending to other paraspinal muscles such as the more laterally located splenium muscle. The third, muscle biopsy demonstrated rimmed vacuoles (RV) in 41% of the 55 patients. RV were more frequently seen in the paraspinal muscles than the limb muscles, where marked myopathic changes of endomysial fibrosis and increased variation of the muscle fiber size were recognized. Based on the anatomical analysis of the paraspinal muscles, alligator sign, a radiological finding of the posterior opening between the cervical spine C1 and C2, seemed to result from the shortening of the cervical semispinal muscle due to its degeneration. This sign may, however, disappear as the whole paraspinal muscles including the semispinal muscles are affected. The RV seen in RSS seems to be a secondary, nonspecific structure related to the muscle degeneration. On the other hand, the above findings, namely the atrophy of SCM, restrictive ventilatory failure, and RV, have not been reported in Emery-Dreifuss muscular dystrophy (EDMD) so far. Accordingly, those findings and the absence of cardiac conduction abnormality are valuable for differential diagnosis of RSS from EDMD.

Adult↗

PubMed1995

Decrease of medullary catecholaminergic neurons in multiple system atrophy and Parkinson's disease and their preservation in amyotrophic lateral sclerosis.

We investigated the number of tyrosine hydroxylase (TH)-immunoreactive neurons in the C1 and A2 regions of the medulla, the sites of the baroreflex arc, in 7 patients with multiple system atrophy (MSA), 8 with Parkinson's disease (PD), 9 with amyotrophic lateral sclerosis (ALS), and 12 age-matched normal subjects to analyze the relationship between cardiovascular dysfunction and medullary catecholaminergic neurons. Orthostatic hypotension (OH) was marked in all the MSA patients and moderate in three PD patients. Three of the five ALS patients who had been on respirators showed lability of blood pressure; paroxysmal hypertension and nocturnal hypotension without compensatory tachycardia. All the MSA patients showed extremely marked decrease of TH-immunoreactive neurons in both the C1 and A2 regions. In the patients with Parkinson's disease, numerous TH-immunoreactive neurons contained Lewy bodies that were immunostained by antibody to TH. TH-immunoreactive neurons were decreased very markedly in the A2 regions of two patients with OH, and three patients without OH showed fairly marked decreases in the C1 or A2 region. In contrast, the number of TH-immunoreactive neurons in ALS was the same as in normal subjects. In MSA and some PD patients, orthostatic hypotension may partly be due to the involvement of the medullary catecholaminergic neurons. The lability of blood pressure in ALS probably is not related to the medullary catecholaminergic neurons.

Aged↗

PubMed1995

Adjuvant chemoimmunotherapy for hepatocellular carcinoma patients. Adriamycin, interleukin-2, and lymphokine-activated killer cells versus adriamycin alone.

To determine improved postresection survival in patients with hepatocellular carcinoma, two postoperative protocols were compared: adoptive chemoimmunotherapy versus chemotherapy. Following resection, 24 patients were allocated at random to receive (1) arterial infusion of Adriamycin, recombinant interleukin-2 and lymphokine-activated killer cells or (2) arterial infusion of Adriamycin alone. The spleen was removed at operation and used to prepare lymphokine-activated killer cells. Each group had 12 patients. They were followed until signs of recurrence appeared. The overall survival rates of the patients were 91.7%, 82.9%, and 72.5% at 1, 2, and 3 years, respectively, and slightly higher than would be expected with surgery alone. No statistically significant difference was found between the two groups either in the survival rate (generalized Wilcoxon test, P = .936) or in the cumulative disease free rate (P = .182). However, when patients who had had hepatic resection with negative margin (> or = 1 cm) were separated, the 2-year cumulative disease-free rate in the adoptive chemoimmunotherapy was higher (83.3%, n = 6) than that in chemotherapy (37.5%, n = 8). Toxicity to adoptive chemoimmunotherapy was moderate; no severe side effects were observed. Totally no statistical difference between the two groups was found. Although only one of six patients in adoptive chemoimmunotherapy experienced recurrence after hepatic resection with negative margin, it was not feasible to determine the role of interleukin-2 and lymphokine-activated killer cells. We conclude that the adoptive chemoimmunotherapy in this study is not an ideal adjuvant protocol after hepatic resection.

Aged↗

PubMed1995

Age-related, different clinicopathologic features of hepatocellular carcinoma patients.

OBJECTIVE: The authors attempted to clarify the clinicopathologic differences of hepatocellular carcinoma (HCC) patients, according to age distribution, and to investigate whether these differences contribute a certain hepatocarcinogenesis. SUMMARY BACKGROUND DATA: Hepatitis-associated viruses causing HCC have been investigated, and the infection of the viruses and etiologically, the peak age of the disease vary according to geographic barriers. However, a correlation between clinicopathologic differences and the age distribution of the patients is not well understood. METHODS: The authors reviewed their institutional experience from 1978 to 1990 in treating 428 patients with HCC. The carrier rate for hepatitis B surface antigen (HBsAg), the frequency of occurrence of high serum alpha-fetoprotein (AFP) of 2000 ng/mL, the degree of liver damage represented by the retention rate of indocyanine green dye at 15 minutes (ICGR15), and the incidence of accompanying liver cirrhosis were investigated and compared in each decade of age. RESULTS: The HBsAg carrier rate and the frequency of high serum AFP values were significantly prominent in the younger patients (20-49 yrs). The degree of liver damage and the incidence of liver cirrhosis were prominent in the elderly patients (older than 70 yrs) or the middle-aged patients (50-69 yrs); however, these four values in the middle-aged patients were intermediate with respect to those observed in the other two age groups. In addition, there was a positive correlation between the HBsAg carrier rate and the frequency of high serum AFP values or between the degree of liver damage represented by ICGR15 and the incidence of liver cirrhosis, showing that the former correlation was inversely related to the latter. CONCLUSIONS: The authors' study indicates that there are age-related differences of clinicopathologic features in HCC patients, suggesting that there are different steps or mechanisms of hepatocarcinogenesis according to the patient's age-distribution.

Adolescent↗

PubMed1995

[Follicle structure regulates cellular interaction between granulosa and thecal cells in follicular development].

To study ovarian follicular development, we established a procedure to reconstruct a follicular wall in vitro by using three-dimensional collagen gel. Granulosa cells and thecal cells were dissociated from median follicles of porcine ovaries. Isolated thecal cells were embedded in collagen gel and a medium containing isolated granulosa cells was overlaid. A monolayer culture of recombined granulosa and thecal cells in collagen gel was used for the control. To examine the synergism of granulosa cells and thecal cells in this culture system, isolated granulosa and thecal cells were cultured either singly or in combination. The culture media were assayed for steroids by RIA. Cultured granulosa cells in this culture system were epitheloid and grown in multilayer aggregates. In contrast, cells cultured by the conventional method were as flat as a monolayer sheet. Ultrastructural findings for these cells showed abundant organella. Gap junctions were often observed between these cells and the basal lamina-like structure. Estradiol production by both culture methods was significantly higher than the sum of that produced by granulosa and thecal cells cultured separately. Androstenedione accumulation was increased by this culture system, but was suppressed by the conventional culture system. These findings suggest that the constitution of the ovarian follicular wall plays an important role in morphological and functional interaction between granulosa and thecal cells.

Animals↗

PubMed1994

Cyclic hexapeptide endothelin receptor antagonists highly potent for both receptor subtypes ETA and ETB.

A cyclic hexapeptide, cyclo(-D-Asp-Trp-Asp-D-Leu-Leu-D-Trp-), designed from cyclo(-D-Glu-Ala-D-alloisoleucyl-Leu-D-Trp-), an ETA receptor-selective antagonist, possessed not only affinity similar to that of BQ-123 for ETA but also higher affinity for ETB than BQ-123. Further modification led to the discovery of cyclo(-D-Asp-Asp(Php)-Asp-D-Thg-Leu-D-Trp-) (Asp(Php): 1-beta-aspartyl-4-phenylpiperazine; Thg: 2-(2-thienyl)glycine) that inhibited [125I]ET-1 binding to the ETA and ETB receptors with IC50 values of 0.082 nM and 120 nM, respectively. Although this compound possesses 1470-fold less affinity for ETB than for ETA, it behaves as a non-selective antagonist that equipotently inhibits vasoconstriction mediated by both receptor subtypes ETA and ETB.

Amino Acid Sequence↗

PubMed1994

Establishment of new SCID and nude mouse models of human B leukemia/lymphoma and effective therapy of the tumors with immunotoxin and monoclonal antibody: marked difference between the SCID and nude mouse models in the antitumor efficacy of monoclonal antibody.

BALL-1, a human B leukemia/lymphoma cell line, was transplanted into nude and SCID mice under various conditions. The transplantation was substantially improved by preadaptation of BALL-1 by serial passages in newborn and young nude mice. We were able to establish the desirable conditions where 100% of SCID and nude mice that were inoculated i.p. with various doses of the adapted BALL-1 (termed BALL-1a) developed tumors. Tumors in SCID mice were disseminated to various tissues in a manner analogous to tumors in patients with B leukemia/lymphoma, whereas tumors in nude mice were not as widely disseminated and grew mainly as ascites. Flow cytometric analyses showed that all of the 11 tested cell surface markers of the parental BALL-1 were well maintained on the tumor cells recovered from the SCID and nude mice. The utility of the developed tumor models for the therapeutic studies was investigated by i.p. or i.v. administration of an anti-B leukemia/lymphoma monoclonal antibody, termed SN7 (IgG1 kappa), and SN7 immunotoxin (IT) that was prepared by conjugating SN7 to ricin A chain (RA) or deglycosylated RA (dgRA). In the nude mouse model study, SN7-RA that had been administered i.p. suppressed the tumor growth completely in all of the treated mice (n = 5) without any sign of tumor or undesirable side effects for as long as followed (i.e., 350 days), whereas unconjugated SN7 showed only a slight therapeutic effect. A control RA conjugate was not effective. In the SCID mouse model studies, several sets of experiments were carried out by i.p. or i.v. administration of IT, monoclonal antibody, or control IT. In the first three sets of experiments, SCID mice inoculated with 1.1 x 10(6) BALL-1a cells received an i.p. administration of phosphate-buffered saline or three different doses (i.e., 4 x 10 micrograms, 4 x 20 micrograms, and 4 x 30 micrograms) of therapeutic agents (SN7-RA and SN7). Virtually an identical result was obtained from the three experiments. All of the phosphate-buffered saline control group mice (n = 15) died within 35 days post tumor inoculation. In contrast, all of the mice that were treated with SN7-RA (n = 19) or with SN7 (n = 15) survived for as long as followed (i.e., 250 days). However, the unconjugated SN7 was less effective than SN7 IT for tumor suppression in SCID mice that were inoculated with a larger tumor burden (i.e., 4 x 10(7) BALL-1a cells).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Participation of the limbic system and its associated areas in the dementia of amyotrophic lateral sclerosis.

The topographic distribution of degenerative changes in large brain sections from five sporadic amyotrophic lateral sclerosis (ALS) patients with dementia and three without dementia was examined. The dementia characteristics were impaired shifting from one line of thinking to another, perseveration, and emotional disinhibition as well as impairment of cognition, and judgment. Neuropathological examinations showed definite ALS changes in all the patients studied. In addition, the five patients with dementia showed neuronal loss, gliosis, and sponginess of the superficial layers throughout the cerebral cortices, predominantly in the dorsomedial cortex of the temporal tip and the parahippocampal, ambiens, anterior cingulate, rectal, orbital, and insular gyri as well as neuronal loss in the basolateral nucleus of the amygdala, nucleus accumbens, and subiculum of the hippocampus. Ubiquitin-immunoreactive inclusions were present in some neurons in the granular cell layers of the hippocampus. Fibrous gliosis was extensive in the subcortical and deep white matter of the frontotemporal lobes. The affected regions take in the limbic system and its associated areas which are the sources of the psychological problems, including emotional disturbance, experienced by these ALS patients. The psychological problems of ALS need to be investigated in relation to the involvement of the limbic system.

Adult↗

PubMed1994

[MRI imaging of purulent cerebral ventriculitis].

This report concerns a 68-year-old male who was diagnosed as having purulent ventriculitis based on CT and MRI findings. He was first admitted to a nearby hospital with fever and impaired consciousness and thought to be suffering from herpes simplex encephalitis based on laboratory findings. In spite of treatment with acyclovir and antibiotics, his symptoms persisted for one and a half months. Because of gradual deterioration of his neurological status, he was transferred to our hospital. On admission he was stuporous with nuchal rigidity and a fever of 38.5 degrees C. The CSF leukocyte count was elevated (217/mm3) with predominantly polymorphonuclear cells (mononuclear 20, polymorphonuclear 197). Gd-DTPA MRI (T1-weighted) showed marked enhancement of the ependyma of the fourth ventricle and both lateral ventricles. A diagnosis of purulent ventriculitis was made and high-dose antibiotics (ABPC 12g, CTX 9g) were started intravenously. Gradual improvement in the clinical signs was observed with rapid normalization of the CSF cell-count. The patient had completely recovered one month after the start of treatment and this was associated with disappearance of abnormal enhancement on the MRI images. Although cerebral ventriculitis occasionally occurs as a complication of neonatal meningitis, it is rare in adult purulent meningitis. In our patient, persistent meningitis combined with impaired drainage of CSF from the ventricles are presumed to have caused ventriculitis. Serial enhanced MRI is particularly helpful in diagnosing ventriculitis, and can serve as a good index for monitoring the effects of treatment.

Aged↗

PubMed1994

[Progress in targeting therapy for hepatic cancer].

Targeting therapy for hepatic cancer is divided into a method using Lipiodol as drug carrier and a method employing immunological responses of monoclonal antibodies to the tumor antigens. For the latter method, immuno-conjugates of antibodies and cytotoxic agents have been studied. Because of the lower response rates of conventional chemotherapy. Lipiodol as drug carrier provides the most effective targeting therapy on hepatic cancer at the present time. Immunotherapy using cytotoxic cells, however, did not result in sufficient clinical efficacy on the liver cancer. The system for accumulation of the effective and sufficient number of cytotoxic cells or immunoconjugates in the targeting tumor tissues are expected to be investigated.

Antibodies, Monoclonal↗

PubMed1993

Establishment and characterization of the tumors of chronic lymphocytic leukemia cell line in nude and SCID mice.

A new cell line, designated MO1043, was established from the peripheral blood (PB) of a patient with B-cell chronic lymphocytic leukemia (CLL). Both the PB leukemia cells and MO1043 were found to have an abnormal cytogenetic marker of trisomy 12, the most common cytogenetic abnormality in CLL. In addition, both the PB cells and MO1043 expressed a cell surface phenotype of typical B-CLLs. The MO1043 was efficiently transplanted into X-irradiated athymic nude mice by i.p. inoculation after it was subjected to serial passages in new born (1 week old) and irradiated adult nude mice. The tumor of a CLL cell line (termed CLL tumor) was also generated in the nude mice by s.c. inoculation of the cells. The MO1043 was inoculated i.p. into mice with severe combined immunodeficiency (SCID) which had not been subject to any preconditionings. The CLL tumor in the non-conditioned SCID mice was disseminated to various tissues in a manner more analogous to CLL tumors in patients as compared with nude mice, where the CLL tumors were not as widely disseminated. At each of four different tumor doses, i.e. 2 x 10(6), 6 x 10(6), 1.8 x 10(7) and 5.4 +/- 10(7) cells of MO1043, the transplantability was 100%. Titration experiments revealed a reciprocal relationship between survival and the number of tumor cells inoculated. FACS analysis showed that several cell surface markers of the parental MO1043 were maintained in CLL tumors from nude and SCID mice. Fluorescence in situ hybridization with novel DNA probes demonstrated that CLL tumors of both nude and SCID mice maintained trisomy 12. The CLL tumor models developed here, particularly the SCID mouse model, may be very useful for therapeutic studies of CLL.

Aged↗

PubMed1993

Rigid spine syndrome and nocturnal alveolar hypoventilation.

A 17-year-old Japanese woman with rigid spine syndrome (RSS) presented with respiratory failure leading to CO2 narcosis. The clinical symptoms were drowsiness, asterixis and cardiac arrhythmias. Tracheostomy and temporary ventilatory support abolished these symptoms. However, polygraphic sleep studies without a ventilator revealed Cheyne-Stokes respiration and profound arterial oxygen desaturation during rapid eye movement sleep. Nocturnal ventilatory support improved not only nocturnal hypoxemia, but daytime blood gas values during spontaneous breathing. These findings indicate that the onset of respiratory failure is preceded by severe nocturnal hypoxemia and that the evaluation and control of nocturnal respiratory insufficiency is essential for RSS patients.

Adolescent↗

PubMed1993

[Rhabdomyolysis associated with pseudohypoparathyroidism type Ib--a case report].

An 18-year-old Japanese female with pseudohypoparathyroidism (PHP) type Ib presented with rhabdomyolysis. The patient, who had been tired after long-distance hiking, experienced paresthesiae and subsequent muscle cramps of the four extremities after drinking a small quantity of alcohol. An occurrence of rhabdomyolysis was confirmed by marked elevation of serum CK activities and muscle necrosis revealed by both CT scanning and biopsy. The exertion and alcohol intake probably induced the initial muscle injury. Subsequently, the muscle necrosis might have worsened the asymptomatic hypocalcemia and decreased 1,25-(OH)2 vitamin D synthesis in PHP type Ib, which resulted in severe muscle cramps and further muscle destruction.

Adolescent↗